Ming-Hai Tang

Publications of Ming-Hai Tang

• Comparative proteomic analysis of atrial appendages from rheumatic heart disease patients with sinus rhythm and atrial fibrillation.

  Authors: Wen-Jun Huang, Rui Zhou, Xiao-Rong Zeng, Xiao-Qiu Tan, Zhi-Hui Cheng, Ming-Hai Tang, Lan-Tu Gou, Li-Juan Chen, Ai-Ping Tong, Yong He, Jin-Liang Yang

  Molecular medicine reports. 03/2011; 4(4):655-61.

  Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice, and contributes to cardiovascular morbidity and mortality. Despite significant advances in theAtrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice, and contributes to cardiovascular morbidity and mortality. Despite significant advances in the understanding of the mechanisms associated with AF, the number of effective biomarkers and viable therapeutic targets remains relatively limited. In this study, 2-DE and MS/MS analysis was used to identify differentially expressed proteins in human atrial appendage tissues from patients with AF (n=4) compared to controls with sinus rhythm (SR; n=5). All subjects had rheumatic heart disease. Following 2-DE analysis, Coomassie Brilliant Blue staining and MS/MS identification, a total of 19 protein spots were found to be differentially expressed between the AF and SR groups. By cluster and metabolic/signaling pathway analysis, these proteins were divided into three major groups: proteins involved in the cytoskeleton and myofilament, energy metabolism associated proteins, and proteins associated with oxidative stress. The proteins identified in this study may enable a better understanding of the molecular mechanisms of AF, and may provide useful biomarkers and novel targets for drug development.

• Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma.

  Authors: Xing-chen Peng, Feng-ming Gong, Yu-wei Zhao, Liang-xue Zhou, Ying-wei Xie, Hong-li Liao, Hong-jun Lin, Zhi-yong Li, Ming-hai Tang, Ai-ping Tong

  PloS one. 01/2011; 6(11):e27309.

  Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For aLung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE) based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05) were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1), significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05). In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma.

• [Quantitative determination of ginsenoside Re and Rg1 in human plasma by ultra performance liquid chromatography-tandem mass spectrometry]

  Authors: Xia Li, Ming-Hai Tang, Fan Zhang, Zhu Yuan, Li-Juan Chen, Xian-Huo Wang

  Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 09/2009; 40(5):912-7.

  OBJECTIVE: To develop a rapid and sensitive method for the pharmacokinetic study of ginsenoside Re and Rg1 in SHEN-FU injective powder in human plasma by Ultra Performance LiquidOBJECTIVE: To develop a rapid and sensitive method for the pharmacokinetic study of ginsenoside Re and Rg1 in SHEN-FU injective powder in human plasma by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC/ESI/MS/MS). METHODS: A Waters C18 column (1.7 microm, 2.1 x 100 mm) was used in this study. The detection of Re and Rg1 was performed on a triple-quadruple mass spectrometer with multiple-reaction monitoring (MRM) mode using the following transitions: m/z 969.6-->789.3 for Re; m/z 823.5-->643.2 for Rg1 and m/z 803.5-->387.1 for digoxin. A total of 324 plasma samples from 18 healthy volunteers were tested. RESULTS: A total run could be accomplished in 4 minutes. Only 50 microL plasma sample was needed to detect Re and Rg1. The lowest detectable concentration for both Re and Rg1 was 0.025 ng/mL. Good linearity appeared from 0.1 to 200 ng/mL (r2>0.999). The decline of Re and Rg1 in plasma could be described by a triple-compartment model. CONCLUSION: The proposed method provides a rapid and sensitive method for the quantification of Re and Rg1 in human plasma, which has been successfully applied to the pharmacokinetic study on intravenous infusion of SHEN-FU powder.

• Altered protein-expressing profile in hPNAS4-induced apoptosis in A549 human lung adenocarcinoma cells.

  Authors: Lan-Tu Gou, Ai-Ping Tong, Fei Yan, Zhu Yuan, Fei He, Wei Wang, Yan Zhou, Li-Juan Chen, Ming-Hai Tang, Jin-Liang Yang

  Journal of cellular biochemistry. 09/2009;

  Human PNAS4 (hPNAS4) is a recently identified pro-apoptosis gene, which is able to induce apoptosis in A549 human lung adenocarcinoma cells following its overexpression. In this work, we investigatedHuman PNAS4 (hPNAS4) is a recently identified pro-apoptosis gene, which is able to induce apoptosis in A549 human lung adenocarcinoma cells following its overexpression. In this work, we investigated the changes of protein profile in hPNAS4-induced apoptosis in A549 cells through proteomic strategy consisting of two-dimensional electrophoresis (2-DE) coupled with MALDI-Q-TOF mass spectrometry. A total of 20 different proteins with more than 3.0-fold change in expression, including 5 up-regulated and 15 down-regulated proteins were successfully identified by database search. The mRNA transcription levels of the different proteins were further examined by RT-PCT. Functional analyses showed these different proteins are involved in diverse biological processes including metabolism, proteolysis, signal transduction, apoptosis, and redox regulation. Two essential apoptosis-associated protein, annexin A1 and prothymosin alpha, were confirmed by Western blot and showed consistent changes with proteomic detection. Our data provide molecular evidence and possible associated pathway in hPNAS4-induced apoptosis through proteomic strategy, which should be contributed to further investigation on biological function of hPNAS4. J. Cell. Biochem. (c) 2009 Wiley-Liss, Inc.

• Liposomal honokiol, a potent anti-angiogenesis agent, in combination with radiotherapy produces a synergistic antitumor efficacy without increasing toxicity.

  Authors: Jia Hu, Li-Juan Chen, Li Liu, Xiang Chen, Ping Li Chen, Guang Yang, Wen-li Hou, Ming-Hai Tang, Fan Zhang, Xian-Huo Wang, Xia Zhao, Yu-Quan Wei

  Experimental & molecular medicine. 01/2009; 40(6):617-28.

  Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay inHonokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC(50) Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy.

• Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft tumor model.

  Authors: Jing Wen, A-Fu Fu, Li-Juan Chen, Xing-Jiang Xie, Guang-li Yang, Xian-Cheng Chen, Yong-Sheng Wang, Jiong Li, Ping Chen, Ming-Hai Tang, Xi Ming Shao, You Lu, Xia Zhao, Yu-Quan Wei

  International journal of cancer. Journal international du cancer. 01/2009;

  Lymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role inLymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role in promoting tumor metastasis to regional lymph nodes and these processes can be inhibited by inactivation of the VEGFR-3 signaling pathway. Honokiol has been reported to possess potent antiangiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor-associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we established lymph node metastasis models by injecting overexpressing VEGF-D Lewis lung carcinoma cells into C57BL/6 mice to explore the effect of honokiol on tumor-associated lymphangiogenesis and related lymph node metastasis. The underlying mechanisms were systematically investigated in vitro and in vivo. In in vivo study, liposomal honokiol significantly inhibited the tumor-associated lymphangiogenesis and metastasis in Lewis lung carcinoma model. A remarkable delay of tumor growth and prolonged life span were also observed. In in vitro study, honokiol inhibited VEGF-D-induced survival, proliferation and tube-formation of both human umbilical vein endothelial cells (HUVECs) and lymphatic vascular endothelial cells (HLECs). Western blotting analysis showed that liposomal honokiol-inhibited Akt and MAPK phosphorylation in 2 endothelial cells, and downregulated expressions of VEGFR-2 of human vascular endothelial cells and VEGFR-3 of lymphatic endothelial cells. Thus, we identified for the first time that honokiol provided therapeutic benefit not only by direct effects on tumor cells and antiangiogenesis but also by inhibiting lymphangiogenesis and metastasis via the VEGFR-3 pathway. The present findings may be of importance to investigate the molecular mechanisms underlying the spread of cancer via the lymphatics and explore the therapeutical strategy of honokiol on antilymphangiogenesis and antimetastasis. (c) 2008 Wiley-Liss, Inc.

• Comparative plasma membrane-associated proteomics of immortalized human hepatocytes.

  Authors: Lan-Tu Gou, Ai-Ping Tong, Li-Juan Chen, Ming-Hai Tang, Bin Chen, Shu-Fang Liang, Canhua Huang, Yu-Quan Wei

  Biochemistry. Biokhimii͡a. 12/2008; 73(11):1200-6.

  This work was initiated with the purpose of purifying and identifying differentially expressed plasma membrane-associated proteins between human liver cancer cell line HepG2 and normal liver cellThis work was initiated with the purpose of purifying and identifying differentially expressed plasma membrane-associated proteins between human liver cancer cell line HepG2 and normal liver cell line L02. The combined strategy of sucrose density gradient centrifugation and subsequent phase partition was applied to obtain high-purity proteins of plasma membrane. Two-dimensional gel electrophoresis revealed the differential protein profile between the two cell lines. A total of 13 plasma membrane-associated proteins containing 10 up-regulated proteins and three down-regulated proteins in HepG2 cells were successfully identified by MALDI-Q-TOF mass spectrometry; they participate in multiple biological functions such as adhesion, proliferation, apoptosis, and signal transduction. The identified proteins could provide helpful reference in clinical investigations on potential candidates for diagnosis and therapy of liver cancer.

• Simultaneous quantitation of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetics evaluation of "SHEN-FU" injectable powder.

  Authors: Fan Zhang, Ming-Hai Tang, Li-Juan Chen, Rui Li, Xian-Huo Wang, Jun-Guo Duan, Xia Zhao, Yu-Quan Wei

  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 08/2008;

  A rapid, specific and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids, i.e. aconitine (AC),A rapid, specific and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids, i.e. aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA) in human plasma collected from 18 healthy volunteers after intravenous drop infusion of "SHEN-FU" injectable powder in three different dosages. Lappaconitine was selected as the internal standard (IS). LC/MS/MS system coupled with an electrospray ionization (ESI) source was performed in multiple-reaction monitoring (MRM) mode. The transitions of the Aconitum alkaloids executed as following: m/z 646.3-->586.0 for AC; m/z 632.4-->573.1 for MA; m/z 616.2-->556.1 for HA; m/z 604.2-->104.8 for BAC; m/z 590.1-->104.8 for BMA; m/z 574.1-->104.8 for BHA; m/z 585.2-->161.8 for IS. Sample preparation was performed with solid-phase extraction (SPE) on a 1mL HLB cartridge prior to analysis. The separation was applied on a Waters C(18) column (1.7mum, 2.1mmx100mm) and a gradient elution of methanol and 0.1% formic acid-water was used as mobile phase. The retention time was less than 4.5min. The concentrations ranged from 0.1 to 1000ng/mL for all six Aconitum alkaloids and showed a good linearity with the correlation coefficient (r(2)) >0.995. The validated method was employed to simultaneous quantitation and successfully used for the first time for the pharmacokinetic evaluation of the six Aconitum alkaloids after intravenous drop administration of "SHEN-FU" injectable powder in phase I clinical trial.

• Comparative proteomics and correlated signaling network of rat hippocampus in the pilocarpine model of temporal lobe epilepsy.

  Authors: Xin-Yu Liu, Jin-Liang Yang, Li-Juan Chen, Ying Zhang, Ming-Li Yang, Yong-Yang Wu, Fu-Qiang Li, Ming-Hai Tang, Shu-Fang Liang, Yu-Quan Wei

  Proteomics. 03/2008; 8(3):582-603.

  In temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation. The pilocarpine-induced TLE provides a model to investigate the molecular and functionalIn temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation. The pilocarpine-induced TLE provides a model to investigate the molecular and functional characterization of epileptogenesis by mimicking the human epileptic condition. Here, we employed a 2-D gel-based proteomic technique to profile proteome changes in the rat hippocampus after pilocarpine treatment. Using MALDI MS and MS/MS, 57 differentially expressed proteins were identified, which were found either up-regulated and/or down-regulated at the two time points 12 h (acute period; Ap) and 72 h (silent period; Sp) compared with the control. These proteins can be related to underlying mechanism of pilocarpine-induced TLE, indicating cytoskeleton modification, altered synaptic function, mitochondrial dysfunction, changed ion channel, and chaperone. Five of the identified proteins, synaptosomal-associated protein 25 (SNAP25), synapsin-2 (SYN2), homer protein homolog 2 (HOMER2), alpha-internexin (INA), and voltage-dependent anion channel 2 (VDAC2) were investigated by semiquantitative RT-PCR, and SNAP25 and INA were further validated by Western blot and immunohistochemistry staining. Furthermore, association of these pilocarpine-induced proteins with biological functions using the Ingenuity Pathway Analysis (IPA) tool showed that nucleic acid metabolism, system development, tissue and cell morphology were significantly altered. IPA of the canonical networks indicated that six membrane proteins (e.g., SNAP25, SYN2, and HOMER2) participated in three biological networks as starting proteins. Our results offer a clue to identify biomarkers for the development of pharmacological therapies targeted at epilepsy.

• Soluble expression of human DRR1 (down-regulated in renal cell carcinoma 1) in Escherichia coli and preparation of its polyclonal antibodies.

  Authors: Xin-Yu Zhao, Hong-Xia Li, Shu-Fang Liang, Zhu Yuan, Fei Yan, Xu-Zhi Ruan, Jia You, Shao-Quan Xiong, Ming-Hai Tang, Yu-Quan Wei

  Biotechnology and applied biochemistry. 02/2008; 49(Pt 1):17-23.

  Human DRR1 (down-regulated in renal cell carcinoma 1) is widely expressed in normal tissues but dramatically reduced or even undetectable in a number of different cancer cell lines and primary tumourHuman DRR1 (down-regulated in renal cell carcinoma 1) is widely expressed in normal tissues but dramatically reduced or even undetectable in a number of different cancer cell lines and primary tumour types. DRR1 from Homo sapiens was cloned into the pQE30 vector for fusion-protein expression with six histidine residues in Escherichia coli BL21(DE3). A soluble protein with a molecular mass of approx. 19 kDa on SDS/PAGE that matches the expected rDRR1 (recombinant DRR1) molecular mass (18.7 kDa) was obtained. The soluble and insoluble expression of recombinant protein DRR1 (rDRR1) was temperature-dependent. The expression rDRR1 was in soluble and insoluble forms at 37 degrees C, and approx. 80% of total rDRR1 was soluble at 37 degrees C, while rDRR1 was almost exclusively expressing in soluble form at 20 degrees C. The expressed rDRR1 at 20 degrees C was affinity-purified on Ni(2+)-charged resin under native conditions. The purified protein was further identified by ESI-MS (electrospray ionization MS). The purified recombinant protein rDRR1 was further used to raise anti-(human DRR1) polyclonal antibodies, which were suitable for detecting both the recombinant exogenous DRR1 and the endogenous DRR1 from tissues and cells by immunoblotting and immunohistochemistry. The purified rDRR1 and our prepared anti-(human DRR1) polyclonal antibodies may provide useful tools for future biological function studies on DRR1.

• [Nano ultra high performance liquid chromatography coupled with time-of-flight mass spectrometer for detecting low molecular weight polypeptides in zebrafish embryos]

  Authors: Han-Shuo Yang, Ming-Hai Tang, Hong-Xin Deng, Jin-Liang Yang

  Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 12/2007; 38(6):1033-6.

  OBJECTIVE: To apply the nano-ultra high performance liquid chromatography coupling with time-of-flight mass spectrometer (nano-UPLC-TOF-MS) to detect the low molecular weight polypeptides inOBJECTIVE: To apply the nano-ultra high performance liquid chromatography coupling with time-of-flight mass spectrometer (nano-UPLC-TOF-MS) to detect the low molecular weight polypeptides in zebrafish embryos. METHODS: Zebrafish embryos were collected 24 hours after fertilization and the outer chorion was removed. And then the yolk was removed with mechanical forces, of which the efficiency was validated by microscope and SDS-PAGE; the low molecular weight polypeptide was extracted with corresponding solution, and followed by separation and detection with nano-UPLC-TOF-MS. RESULTS: Mechanical vortex almost completely removed yolk cells of zebrafish embryos, from which the special solution extracted effectively low molecular weight polypeptides for the later detection. As demonstrated by nano-UPLC-TOF-MS, the polypeptide peak showed between 22 and 24. 5 min, and the m/z ration of most of polypeptides were between 800-1400. CONCLUSION: Nano-OPLC-TOF-MS is effective to detect low molecular weight polypeptides, and low molecular weight peptides definitely exist in zebrafish embryos, of which the relative molecular mass seems to be 800 to 1400, probably consists of about 10 residues.

• [Nanoliposomal quercetin inhibits formation of malignant ascites of hepatocellular carcinoma]

  Authors: Zhi-Ping Yuan, Li-Juan Chen, Yu-Quan Wei, Lin-Yu Fan, Ming-Hai Tang, Guang-li Yang

  Ai zheng = Aizheng = Chinese journal of cancer. 08/2006; 25(8):941-5.

  BACKGROUND & OBJECTIVE: Quercetin is a potential chemotherapeutic drug with many biological activities. However, the insolubility of quercetin seriously limits its clinical use. This study was toBACKGROUND & OBJECTIVE: Quercetin is a potential chemotherapeutic drug with many biological activities. However, the insolubility of quercetin seriously limits its clinical use. This study was to investigate the biodistribution of quercetin encapsulated by pegylated nanoliposomes and its therapeutic efficacy on the formation of carcinomatous ascites of hepatocellular carcinoma in mice. METHODS: Nanoliposomal quercetin was prepared with conventional rotary evaporation method. BALB/c mice inoculated with hepatocellular carcinoma cells (H22) at the anterior right subaxilla for twelve days were given intravascular injection with nanoliposomal quercetin at 1.5 mg/body (based on quercetin) at different time points. Then the levels of quercetin in the plasma, tumor tissues and normal organs were tested by high pressure liquid chromatography (HPLC). Various dosages of nanoliposomal quercetin were peritoneally given to tumor-bearing mice to determine the optimal dose. The tumor-bearing mice were treated intraperitoneally with 100 mg/kg nanoliposomal quercetin once a day for 14 days. The formation of malignant ascites, increase of body weight, survival time and peritoneal capillary permeability were assessed. Apoptotic cells in ascites were detected by flow cytometry. RESULTS: Nanoliposomal quercetin was a spherical particle with 25% drug content (W/W) and 130+/-20 nm in diameter. Nanoliposomal quercetin effectively aggregated in tumor tissues and its half-life period was 4 h. Nanoliposome quercetin inhibited the formation of malignant ascites of hepatocellular carcinoma model in a dose-dependent manner. Moreover, 100 mg/kg nanoliposomal quercetin significantly enhanced the apoptosis of cancer cells in ascites, inhibited the increase of body weight, reduced peritoneal capillary permeability and prolonged the survival time of tumor-bearing mice compared with PBS control. CONCLUSION: Nanoliposomal quercetin can effectively accumulate in tumor tissues and inhibit the formation of malignant ascites, thus it might be used as a potential antitumor drug which deserves future study.

• Liposomal quercetin efficiently suppresses growth of solid tumors in murine models.

  Authors: Zhi-Ping Yuan, Li-Juan Chen, Lin-Yu Fan, Ming-Hai Tang, Guang-li Yang, Han-su Yang, Xiao-Bo Du, Guo-Qing Wang, Wen-Xiu Yao, Qu-mei Zhao, Bin Ye, Rui Wang, Peng Diao, Wei Zhang, Hong-Bin Wu, Xia Zhao, Yu-Quan Wei

  Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2006; 12(10):3193-9.

  PURPOSE: Quercetin is a potent chemotherapeutic drug. Clinical trials exploring different schedules of administration of quercetin have been hampered by its extreme water insolubility. To overcomePURPOSE: Quercetin is a potent chemotherapeutic drug. Clinical trials exploring different schedules of administration of quercetin have been hampered by its extreme water insolubility. To overcome this limitation, this study is aimed to develop liposomal quercetin and investigate its distribution in vivo and antitumor efficacy in vivo and in vitro. EXPERIMENTAL DESIGN: Quercetin was encapsulated in polyethylene glycol 4000 liposomes. Biodistribution of liposomal quercetin i.v. at 50 mg/kg in tumor-bearing mice was detected by high-performance liquid chromatography. Induction of apoptosis by liposomal quercetin in vitro was tested. The antitumor activity of liposomal quercetin was evaluated in the immunocompetent C57BL/6N mice bearing LL/2 Lewis lung cancer and in BALB/c mice bearing CT26 colon adenocarcinoma and H22 hepatoma. Tumor volume and survival time were observed. The mechanisms underlying the antitumor effect of quercetin in vivo was investigated by detecting the microvessel density, apoptosis, and heat shock protein 70 expression in tumor tissues. RESULTS: Liposomal quercetin could be dissolved in i.v. injection and effectively accumulate in tumor tissues. The half-time of liposomal quercetin was 2 hours in plasma. The liposomal quercetin induced apoptosis in vitro and significantly inhibited tumor growth in vivo in a dose-dependent manner. The optimal dose of liposomal quercetin resulted in a 40-day survival rate of 40%. Quantitative real-time PCR showed that liposomal quercetin down-regulated the expression of heat shock protein 70 in tumor tissues. Immunohistochemistry analysis showed that liposomal quercetin inhibited tumor angiogenesis as assessed by CD31 and induced tumor cell apoptosis. CONCLUSIONS: Our data indicated that pegylated liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be a potential application in the treatment of tumor.