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《Chinese Journal of Cancer》 2005-12
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Antitumor Effect and Mechanism of Shikonin Derivative SYUNZ-7

HUANG He1,2, XIE Bing-Fen1,2, ZHU Xiao-Feng1,2, FENG Gong-Kan1,2, ZHOU Jun-Min1,2, WANG Yi1,2, WU Hai-Qiang3, HUANG Zhi-Shu3, GU Lian-Quan3, LIU Zong-Chao1,2 1. State Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong, 510060, P. R. China 2. Research Department, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China 3. School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, 510275, P. R. China  
BACKGROUND OBJECTIVE: Natural shikonin compounds and their derivatives have cytotoxicity and antitumor effects. This study was to explore in vitro and in vivo antitumor effects of SYUNZ-7 [2 or 3, 11-bis(phenylsulfanyl)-6-isohexenylnaphthazarin] and the mechanisms. METHODS: In vitro antiproliferation effects of SYUNZ-7 on human lung adenocarcinoma cell line GLC-82, human nasopharyngeal cancer cell line CNE2, human oral cavity cancer cell line KB, human gastric cancer cell line MGC-803 and human hepatocellular cancer cell line HepG2 were tested by MTT assay. In vivo antitumor effect of SYUNZ-7 was tested using ascitic cancer EAC xenograft in mice and CNE2 xenograft in nude mice models. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The in vivo effect of SYUNZ-7 on angiogenesis was detected by immunohistochemistry. RESULTS: The 50% inhibitory concentrations (IC50) of SYUNZ-7 to GLC-82, CNE2, KB, MGC-803, and HepG2 cells were (2.18±0.04) μg/ml, (4.17±0.09) μg/ml, (5.41±0.10) μg/ml, (6.41±0.14) μg/ml, and (9.99±0.21) μg/ml, respectively. Under the treatment of 1, 2, 4, and 8 mg/kg of SYUNZ-7, the inhibitory rates of EAC xenografts in mice were (40.5±0.14)%, (50.9±2.3)%, (61.7±1.8)%, and (65.6±7.4)%, respectively (P0.01). Under the treatment of 1, 2, and 4 mg/kg of SYUNZ-7, the inhibitory rates of CNE2 xenografts in nude mice were 24.7%, 38.3%, and 41.2%, respectively (P0.05). SYUNZ-7 induced apoptosis of CNE2 cells in time- and concentration-dependent manners, and blocked the transition of CNE2 cells from S to G2/M phase. SYUNZ-7 also inhibited the angiogenesis of CNE2 xenografts in nude mice in a concentration-dependent manner. CONCLUSION: SYUNZ-7 has strong in vivo and in vitro antitumor effects which are related to inducing cell apoptosis, blocking cell cycle, and inhibiting angiogenesis of tumor.
【Fund】: 国家自然科学基金项目(No.30271601 No.20272085)~~
【CateGory Index】: R285
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