埃罗替尼联合培美曲塞序贯化疗对提高胰腺癌细胞敏感性的机制研究

目的 探讨埃罗替尼联合培美曲塞序贯化疗对提高人胰腺癌PANC-1和BXPC-3细胞敏感性的细胞学机制.方法 qPCR-HRM法检测细胞EGFR和K-ras基因突变;实验分为对照组、培美曲塞及埃罗替尼单药组、同时作用组、培美曲塞序贯埃罗替尼组、埃罗替尼序贯培美曲塞组.Western blotting检测各组细胞EGFR、HER3、AKT、c-MET蛋白及磷酸化表达.结果 ① PANC-1细胞K-ras基因2外显子为突变型.②培美曲塞序贯埃罗替尼组p-EGFR、p-HER3、p-AKT与其他各组相比被显著抑制（P〈0.05）.③ c-MET的蛋白及磷酸化表达在各处理组之间均无明显变化.结论 培美曲塞可上调p-EGFR、p-HER3、p-AKT磷酸化水平,使后续埃罗替尼敏感性增强是序贯协同增效作用的机制之一,为两者联合治疗晚期胰腺癌提供理论依据.

Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in BXPC-3 and PANC-1 human pancreatic cancer cells

Objective To assess the cellular mechanism of schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in BXPC-3 and PANC-1 human pancreatic cancer cells. Methods The EGFR and K-ras gene mutation were ex- amined by qPCR-HRM. The expression and phosphorylation of EGFR, HER3, AKT and c-MET were determined by West- ern blotting. Results The EGFR gene of PANC-1 and BXPC-3 cells were wlde-type and PANC-1 cells harbored a specific mutation in K-ras exon. p-EGFR, p-HER3 and p-AKT in sequential erlotinib pemetrexed group were significantly inhibi- ted compared with other groups （P 〈 0.05）. The results showed that there was no significant change in the phosphorylation level of MET in different schedules groups. Conclusion The enhanced inhibitory effect of erlotinib following pemetrexed may relate with pemetrexed enhances the antitumor activity of erlotinib by activating the EGFR/HER3/AKT pathway.