AIM: To investigate the effects of artesunate on proliferation and apoptosis in human hepatocelluar carcinoma cell line HepG2 and to study the sensitizing effect of artesunate on HepG2 cells to chemotherapeutic drugs. METHODS: The proliferation of HepG2 cells was determined by the assay of cell counting kit - 8 ( CCK - 8 ) and the colony formation test. The morphology of HepG2 cells with Hoechst 33258 staining was observed under fluorescent microscope. Annexin V/propidium iodide ( PI) was used to analyze the apoptosis and the cell cycle. The sensitizing effects of artesunate on HepG2 cells to chemotherapeutic drugs [ 5 - fluorouracil( 5 - FU ), carboplatin and epirubicin ] were determined by CCK - 8 assay. RESULTS: When treated with artesunate for 48 h, the proliferation of HepG2 cells was significantly inhibited in a dose - dependent manner. The IC50 was 19. 2 μmol/L. Compared with the control cells, the colony formation of HepG2 cells treated with artesunate for 7 days was significantly inhibited. The nuclear fragmentation, karyopy-knosis, chromosomal condensation, cell shrinkage, and attachment loss in HepG2 cells treated with artesunate were observed. The cells in G2 phase increased obviously, and the percentages of hypodiploid cells and early apoptotic rates were significantly higher in artesunate treatment groups than those in control group. The IC50 of 5 - FU, carboplatin and epirubicin combined with artesunate was 3.33, 2.02 and 1.71 times sensitized as compared with control group, respectively.CONCLUSION: Artesunate effectively inhibits proliferation and induces apoptosis of HepG2 cells. Aresunate also sensitizes HepG2 cells to chemotherapeutic drugs.%目的:研究青蒿琥酯对人肝癌HepG2细胞增殖和凋亡的作用,并检测其是否影响HepG2细胞对化疗药物的敏感性.方法:采用CCK-8法观察不同浓度青蒿琥酯对HepG2细胞生长增殖的影响;克隆形成实验检测青蒿琥酯对HepG2细胞克隆形成的影响;Hoechst 33258染色观察青蒿琥酯作用HepG2细胞后细胞形态的变化;PI单染流式细胞术检测青蒿琥酯对HepG2细胞周期以及亚二倍体率的影响;Annexin V-PI双染测定青蒿琥酯对HepG2细胞凋亡的影响;CCK-8法检测青蒿琥酯对HepG2细胞化疗药物敏感性的影响.结果:(1)青蒿琥酯作用于HepG2细胞48 h后,能有效抑制其增殖,随着浓度的升高,增殖抑制率越高,IC50值为19.2 μmol/L.(2)青蒿琥酯作用HepG2细胞7 d后,能有效抑制HepG2细胞形成的克隆数.(3)青蒿琥酯作用于HepG2细胞48 h后,Hoechst 33258染色可见实验组细胞胞核固缩、边聚和裂解、凋亡小体形成等凋亡形态学变化.(4)青蒿琥酯作用于HepG2细胞48 h后,PI单染流式细胞术检测细胞周期发现实验组细胞明显阻滞于G2期.(5)青蒿琥酯作用于HepG2细胞48 h后,PI单染实验检测实验组出现明显的亚二倍体凋亡峰;Annexin V-PI 双染实验检测实验组细胞出现明显的早期凋亡细胞群.(6)青蒿琥酯分别联合化疗药物5-氟尿嘧啶、卡铂和表柔比星作用于HepG2细胞48 h后,能明显增强化疗药物对肿瘤细胞的抑制作用,增敏倍数分别为3.33、2.02和1.71.结论:(1)青蒿琥酯对人肝癌HepG2细胞有增殖抑制作用,并诱导其凋亡.(2)青蒿琥酯能提高人肝癌HepG2细胞对5-氟尿嘧啶、卡铂和表柔比星的敏感性.
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