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ABSTRACT: Fibroblast activation protein (FAP) is a specific serine protease expressed in tumor stroma proven to be a stimulatory factor in the progression of some cancers. The purpose of this study was to investigate the effects of FAP knockdown on tumor growth and the tumor microenvironment. Mice bearing 4T1 subcutaneous tumors were treated with liposome-shRNA complexes targeting FAP. Tumor volumes and weights were monitored, and FAP, collagen, microvessel density (MVD), and apoptosis were measured. Our studies showed that shRNA targeting of FAP in murine breast cancer reduces FAP expression, inhibits tumor growth, promotes collagen accumulation (38%), and suppresses angiogenesis (71.7%), as well as promoting apoptosis (by threefold). We suggest that FAP plays a role in tumor growth and in altering the tumor microenvironment. Targeting FAP may therefore represent a supplementary therapy for breast cancer. [BMB Reports 2013; 46(5): 252-257].
BMB reports 05/2013; 46(5):252-257. · 1.72 Impact Factor
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MaLing Gou,
HuaShan Shi,
Gang Guo,
Ke Men,
Juan Zhang,
Lan Zheng, ZhiYong Li,
Feng Luo,
ZhiYong Qian,
Xia Zhao,
YuQuan Wei
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ABSTRACT: In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.
Nanotechnology 03/2011; 22(9):095102. · 3.98 Impact Factor
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Lina Zhou,
Xingyi Li,
Xiancheng Chen, Zhiyong Li,
Xianping Liu,
Shengtao Zhou,
Qian Zhong,
Tao Yi,
Yuquan Wei,
Xia Zhao,
Zhiyong Qian
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ABSTRACT: Application of camptothecin (CPT) is hampered due to its extreme water insolubility and unpredictable side effects. Therefore, it is essential to establish an efficient and safe protocol for the administration of camptothecin against tumor growth and metastasis. Here, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) and tested it on BALB/c mice subcutaneously injected with murine hepatocellular carcinoma cells at the hindlimb feet pad. CPT-TMC effectively inhibited tumor growth and lymphatic metastasis, prolonged survival time, yet without apparent toxic effects. Thus, CPT-TMC may provide a novel and effective therapeutic strategy against human advanced hepatic cancer without conspicuous systemic toxic effects.
Cancer letters 11/2010; 297(1):56-64. · 4.86 Impact Factor
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Lina Zhou,
Licheng Du,
Xiancheng Chen,
Xingyi Li, Zhiyong Li,
Yuan Wen,
Zhengyu Li,
Xiang He,
Yuquan Wei,
Xia Zhao,
Zhiyong Qian
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ABSTRACT: Lymphatic metastasis plays a critical role in ovarian cancer, indicates poor prognoses and correlates to the majority of cancer deaths. Camptothecin derivatives exhibit promising activity for the treatment of solid tumors because of its specific inhibition of eukaryotic DNA topoisomerase I. Yet, its application is hindered due to extreme water insolubility and severe side effects. It is essential to establish an efficient and safe protocol for the administration of camptothecin versus tumor metastasis and growth. In the current research, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) to increase its water-solubility and lower its side effects, and tested it on a high potential lymphogenous metastatic model of human ovarian cancer. In the prophase study, we successfully transfected SKOV3 cells with VEGF-D recombinant plasmid DNA (pcDNA3.1(+)/VEGF-D) to construct a cell line named SKOV3/VEGF-D and establish a feasible lymphogenous metastatic model. The antitumor and antimetastatic activities of CPT-TMC were evaluated in nude mice subcutaneously inoculated with SKOV3/VEGF-D cells at the left hindlimb claw pad. The tumor-bearing mice were divided randomly into four groups and treated twice per week for three weeks. Evan's Blue Dye was used to delineate functional lymphatic vessels. Lymphatic metastasis rates were detected by hematoxylin and eosin (HE) staining. Expression of VEGF-D and MMP-9 were investigated by immunohistochemistry. In contrast to controls, administration of CPT-TMC achieved effective inhibition in primary tumor volume and lymphogenous metastasis, yet without apparent systemic toxic effects. These effects were associated with simultaneously down-regulated VEGF-D and MMP-9 expression, significantly decreased tumor-associated lymphatic and blood sprouts, tremendously reduced systemic toxic effects, dramatically increased tumor apoptotic index. Our data indicate that CPT-TMC is superior to CPT by maximizing its anticancer and antimetastatic activities with minimal toxicity on hosts. CPT-TMC may become a potentially therapeutic strategy against human advanced ovarian cancer.
Oncology Reports 10/2010; 24(4):941-8. · 1.84 Impact Factor
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Yan Shan,
Chunting Wang,
Li Yang,
Li Juan Chen,
Hong Xin Deng,
Han Shuo Yang,
Zhimian Li, Zhiyong Li,
Li Pan,
Fei Leng,
Yuquan Wei
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ABSTRACT: Anti-apoptosis plays an important role in tumour formation and development. Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a target for anti-cancer drug exploitation was replaced as development. We investigated the role of the homo dominant-negative mutant Survivin-T34A in suppressing human lung adenocarcinomas (A549). The anti-tumour activity of HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing A549 subcutaneous tumours. Low-dose systemic administration was continuously used. The HSurvivinT34A plasmid (5 meu g/one) complexed with a cationic liposome (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed microvessel density degradation by CD31 immunohistochemistry and apoptotic cell increase by TUNEL assay, PI staining and flow cytometric analysis in the treated group. The present findings suggest that the HSurvivinT34A plasmid complexed with a cationic liposome may provide an effective approach to inhibit the growth of human lung adenocarcinomas in vitro and in vivo.
Journal of Biosciences 06/2010; 35(2):209-16. · 1.65 Impact Factor
