目的：探讨苹果酸舒尼替尼对人肝癌HepG2细胞凋亡的作用及其机制。方法：常规体外培养HepG2细胞，利用MTT法检测舒尼替尼杀伤HepG2细胞的IC50，Western blotting 检测药物处理前后HepG2细胞分子靶点蛋白表达，膜联蛋白(Annexin-V)/碘化丙啶(PI)双标法和TUNEL染色法检测舒尼替尼处理前后HepG2细胞凋亡情况，实时荧光定量PCR检测药物处理前后HepG2细胞凋亡基因 mRNA的表达情况。结果：舒尼替尼杀伤HepG2细胞的IC50值为（3.22±0.50）μmol/L。以对HepG2细胞无明显抑制作用的剂量1 μmol/L舒尼替尼处理HepG2细胞后，细胞内VEGFR1、VEGFR2、PDGFRα、Kit、FLT3蛋白表达均有不同水平下降（均P<0.05），HepG2细胞的凋亡率\[(15.18±1.28)% vs (5.90±0.45)%,P<0.05\]、凋亡指数（AI）\[(23.54±4.73) vs (4.17±0.64), P<0.05\]均显著升高。舒尼替尼处理HepG2细胞后，上调促凋亡基因Bax、NOXA、PUMA、P53 mRNA表达水平（均P<0.05)，降低抑凋亡基因Bcl-2、X-IAP mRNA表达水平（均P<0.05）。结论： 舒尼替尼能够诱导肝癌HepG2细胞凋亡，其机制可能是通过上调促凋亡基因的表达及降低抑凋亡基因表达水平来实现的。

Objective:To investigate the apoptotic effect of sunitinib on human hepatocellular carcinoma cell HepG2 and explore the underlying molecular mechanism. Methods: The HepG2 cells were cultivated by routine method. The effect of sunitinib on the growth of HepG2 cells was assessed by MTT assay. Molecular targets in the hepatocellular carcinoma HepG2 cells were examined by immunoblotting. Apoptotic cell death was detected using Annexin-V/PI double labeled flow cytometry and TUNEL assay. The expressions of mRNA were quantitated by RT-qPCR. Results: The IC50 of sunitinib for inhibiting HepG2 cell growth was （3.22±0.50）μmol/L. After exposed to sunitinib, the expression of VEGFR1, VEGFR2, PDGFRα, Kit, FLT3 were decreased in HepG2 cells. Apoptosis rates of HepG2 cells were (5.90±0.45)% vs (15.18±1.28)% in the absence or presence of sunitinib respectively, and corresponding apoptosis index (AI) were (4.17±0.64) vs (23.54±4.73). After treated with sunitinib, the expressions of pro-apoptotic genes Bax, NOXA, PUMA and P53 were increased in the cells, whereas that of apoptosis-inhibiting genes Bcl-2 and X-IAP were significantly decreased.Conclusion: Increased expression of pro-apoptotic genes and decreased apoptosis-inhibiting genes are likely responsible for sunitinib-induced apoptosis in human hepatocellular carcinoma HepG2 cells.

国家自然科学青年基金资助项目（No. 81302372，81300431）；南方医科大学珠江医院优秀中青年人才项目资助（No. 201207008)