目的研究多聚腺苷二磷酸核糖聚合酶-1(PARP-1)抑制剂5-氨基异喹啉酮(5-AIQ)联合化疗药物依托泊苷(VP16)对雄激素非依赖性前列腺癌PC3细胞株增殖的影响。方法 MTS比色法观察不同浓度5-AIQ联合VP16对PC3细胞的增殖抑制作用,并应用WesternBlot法检测应用5-AIQ或VP16及二者联合应用对PC3细胞内PARP-1蛋白表达的影响。结果 MTS结果显示,与单独应用VP16(5μmol/L、25μmol/L或125μmol/L)比较,联合应用5-AIQ(125μmol/L或500μmol/L)可以明显增强VP16对PC3细胞的增殖抑制作用,组间差异均有统计学意义(P〈0.05)。而且当5-AIQ与低剂量VP16(5μmol/L)联合应用时可以达到与高剂量VP16(25μmol/L或125μmol/L)类似甚至更强的增殖抑制作用。WesternBlot结果显示,与对照组比较,5-AIQ(250μmol/L)或VP16(50μmol/L或100μmol/L)均可以明显下调PC3细胞内源性PARP-1的表达(P〈0.05)。与二者单一处理组(5-AIQ,250μmol/L)或(VP16,50μmol/L)相比,二者联合应用可进一步下调PARP-1的表达水平。结论 PARP-1抑制剂5-AIQ可以明显增强VP16对PC3细胞的增殖抑制作用,该作用可能与PARP-1蛋白的表达抑制有关。
Objective To observe the effect of PARP-1 inhibitor 5-AIQ combined with Etoposide VP16 on the proliferation of prostate cancer cell line PC3. Methods MTS assay was employed to analyze the effect of 5-AIQ and/or VP16 on the proliferation of PC3 cell. The expression level of PARP-1 was detected by Western Blot. Results MTS assay showed the combination of 5-AIQ and VP16 could significantly enhance the cytostatic action than VP16 alone (P〈0.05). And the role of cytostatic action when treated with 5-AIQ combined with low-dose VP16 (5 μmol/L) was similar or stronger compared with high-dose VP16 (25 μmol/L or 125 μmol/L). The expression levels of PARP-1 were significantly down-regulated when treated with 5-AIQ or VP16 alone (P〈0.05). A further decrease of PARP-1 was found when treated with the combination of 5-AIQ and VP16. Conclusion 5-AIQ could significantly enhance the cytostatic action of VP16 to PC3 cells, which maybe related to the inhibition of PARP-1 expression.