Guang-li Yang

Publications of Guang-li Yang

• 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.

• [BFGF entraped in cationic liposomes as adjuvant: optimization of technical parameters]

  Authors: Zhen-hua Zhong, Shuang-lin Mao, Li Yang, Guang-li Yang, Wen-li Hou, Xiang Chen, Li-Juan Chen

  Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 10/2008; 39(5):839-41, 846.

  OBJECTIVE: To test the immune efficiency of bFGF entraped in cationic liposomes as adjuvant in vivo. METHODS: The technical parameters on encapsulation were tested in each step to gain highOBJECTIVE: To test the immune efficiency of bFGF entraped in cationic liposomes as adjuvant in vivo. METHODS: The technical parameters on encapsulation were tested in each step to gain high encapsulation efficiencies, which included lipid composition, weight ratio of protein and lipids, liposome extrusion, and different conditions of freeze-thawing. The bFGF in cationic liposome, Freund's adjuvant, or PBS were injected (four times) to the four-week old Balb/c mice to test the immune responses. The serum antibody was measured by ELISA 13 days after each injection. RESULTS: Maximal encapsulation efficiency (about 50%) was achieved through optimized technical parameters. Cationic liposome demonstrated satisfied immune efficiency as adjuvant. CONCLUSION: Cationic liposome is a safe and effective immunological adjuvant.

• Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model.

  Authors: Qi-Qi Jiang, Lin-Yu Fan, Guang-li Yang, Wen-Hao Guo, Wen-li Hou, Li-Juan Chen, Yu-Quan Wei

  BMC cancer. 09/2008; 8(1):242.

  ABSTRACT: Background Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against humanABSTRACT: Background Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against human lung cancer as well as potentiates the antitumor activity of cisplatin in A549 lung cancer xenograft model, if so, to examine the possible mechanism in the phenomenon. METHODS: Human A549 lung cancer-bearing nude mice were treated with liposomal honokiol, liposomal honokiol plus DDP or with control groups. Apoptotic cells and vessels were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31 respectively. RESULTS: The present study showed that liposomal honokiol alone resulted in effective suppression of the tumor growth, and that the combined treatment with honokiol plus DDP had the enhanced inhibition of the tumor growth and resulted in a significant increase in life span. The more apparent apoptotic cells in the tumors treated with honokiol plus DDP was found in fluorescent in situ TUNEL assay, compared with the treatment with control groups. In addition, the combination of honokiol and DDP apparently reduced the number of vessels by immunolabeling of CD31 in the tissue sections, compared with control groups. CONCLUSIONS: In summary, our data suggest that honokiol alone had the antitumor activity against human lung cancer in A549 lung cancer xenograft model, and that the combination of honokiol with DDP can enhance the antitumor 3 activity, and that the enhanced antitumor efficacy in vivo may in part result from the increased induction of the apoptosis and the enhanced inhibition of angiogenesis in the combined treatment. The present findings may be of importance to the further exploration of the potential application of the honokiol alone or the combined approach in the treatment of lung carcinoma.

• [Effects of honokiol on proliferation and apoptosis of human cervical carcinoma cell line Hela in vitro]

  Authors: Guang-li Yang, Wen-li Hou, A-Fu Fu, Zhen-hua Zhong, Xiu-hua Yin, Li-Juan Chen

  Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 08/2008; 39(4):558-62.

  OBJECTIVE: To assess the effects of honokiol on proliferation and apoptosis of human cervical carcinoma cell line Hela in vitro. METHODS: Cultured HeLa cells were treated with differentOBJECTIVE: To assess the effects of honokiol on proliferation and apoptosis of human cervical carcinoma cell line Hela in vitro. METHODS: Cultured HeLa cells were treated with different concentrations of honokiol for the varieties of period (24, 48, 72, 96 h). Cell proliferation was assessed by MTT colorimetric assay. Cell apoptosis was determined by flow cytometry (FCM), Hoechst 33258 fluorescent staining and DNA ladder respectively. RESULTS: MTT assay demonstrated that the proliferation of Hela cells were suppressed significantly by honokiol in dose-and time-dependent manner. FCM analysis showed that the apoptosis rates of Hela cells treated with 10 microg/mL and 20 microg/mL honokiol for 24 h were 22.5% and 62.2%, respectively, while that of the control group cells was 8.7%. After treatment with honokiol, typically morphologic changes of apoptosis were observed by Hoechst 33258 fluorescence staining; Genomic DNA from Hela cells treated with honokiol displayed a characteristic ladder pattern on agarose gel electrophoresis. CONCLUSION: honokiol can inhibit the proliferation and induce apoptosis of human cervical carcinoma cell line Hela.

• [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.