姜黄素增加HepG2细胞对顺铂敏感性的作用及机制研究

Mechanism of Curcumin on Increasing the Sensitivity of HepG2 Cells to Cisplatin

目的探讨姜黄素对肝癌细胞株HepG2对顺铂敏感性的影响及其作用机制。方法采用不同浓度姜黄素(0、2.5、5、7.5、10μM)及顺铂(10、20、40、80μM)单用或联用处理HepG2细胞株后,通过MTT检测细胞增殖抑制率,流式细胞术检测细胞凋亡情况,Real-time PCR技术检测Survivin、Cyto-C、Bcl2、Bax的基因表达情况;western blot检测Survivin、Cyto-C、cleaved caspase-3、Bcl-2、Bax的蛋白表达。结果姜黄素以浓度依赖性方式抑制HepG2细胞株Survivin的m RNA表达和蛋白表达(P<0.05);姜黄素联合顺铂处理的HepG2细胞增殖抑制率及细胞凋亡率较单用顺铂处理均明显增加(P<0.05);姜黄素联合顺铂可显著抑制Survivin的蛋白表达,降低Bcl-2/Bax比例,增加Cyto-C、cleaved caspase-3蛋白表达(P<0.05)。结论姜黄素可增加HepG2细胞对顺铂的敏感性,可能与其抑制Survivin的表达,降低Bcl-2/Bax比例,增加cleaved caspase-3、Cyto-C蛋白的表达有关。

Objective To explore the mechanisms of curcumin in increasing the sensitivity to cisplatin in HepG2 cells. Methods HepG2 cells were treated with different concentrations of curcumin（0, 2.5, 5, 7.5, 10 μM）, cisplatin（10, 20, 40, 80 μM） alone or in combination. Then cell proliferation rates were detected by MTT, cell apo ptotic rates tested by flow cytometry, Survivin, Cyto-C, Bcl2 and Bax gene an.proein expression examined by Real-time PCR and western blot analysis separately. Results Curcumin inhibited the m RNA and protein expression of Survivin in a concentration-dependent manner in HepG2 cells（P0.05）. Combination treatment of curcumin and cisplatin resulted in a higher proliferation inhibition rate and apoptotic rate in HepG2 cells than cisplatin treatment alone（P0.05）. After curcumin and cisplatin combination therapy, the protein expression level of Survivin and ratio of Bcl-2/Bax were significantly decreased, while expressions of Cyto-C and cleaved caspase-3 were significantly increased（P0.05）. Conclusion Curcumin increases the sensitivity of HepG2 cells to cisplatin by inhibiting the expression of Survivin, reducing the ratio of Bcl-2/Bax, and increasing expression of Cyto-C and cleaved caspase-3.