吉西他滨联合顺铂调控mTOR/S6K1/NF-κB信号治疗乳腺癌的机制研究

Effect of Gemcitabine Combined with Cisplatin on mTOR/S6K1/NF-κB Signaling in the Treatment of Breast Cancer

目的探讨吉西他滨联合顺铂调控mTOR/S6K1/NF-κB信号治疗乳腺癌的机制。方法选取150例女性原发性乳腺癌患者接受吉西他滨联合顺铂化疗2疗程后评价疗效。采用免疫组织化学法检测乳腺癌患者癌组织中mTOR、S6K1和NF-κB蛋白的表达;采用Real-Time PCR法和Western Blot法检测乳腺癌组织中mTOR、S6K1和NF-κB mRNA和蛋白的表达; ELISA法检测患者p65、BCL-2和Caspase 3含量。结果与吉西他滨和顺铂化疗前相比,患者血清CA15-3、CA125和NSE水平均降低,且差异具有统计学意义(P <0.05)。与化疗前相比,化疗后乳腺癌组织中mTOR和S6K1蛋白含量和mRNA表达显著降低(P <0.05),NF-κB蛋白含量和mRNA表达显著上升(P <0.05);患者p65和Caspase 3表达含量显著增加(P <0.05),BCL-2的表达量显著降低(P <0.05)。结论吉西他滨联合顺铂化疗对乳腺癌有一定的临床治疗作用,且mTOR/S6K1/NF-κB信号通路在化疗过程中发挥重要的作用。

Objective To investigate the mechanism of gemcitabine combined with cisplatin in the regulation of mTOR/S6K1/NF-κB signaling in breast cancer. Methods 150 patients with primary breast cancer admitted to our hospital 2016/3-2017/5 were treated with gemcitabine combined with cisplatin chemotherapy for 2 courses.Immunohistochemical method was used to detect the expression of mTOR,S6K1 and NF-κB protein in breast cancer patients.The expression of mTOR,S6K1 and NF-κB mRNA and protein in breast cancer tissues were detected by Real-Time PCR and Western Blot.The levels of p65,BCL-2 and Caspase 3 were detected by ELISA. Results Compared with gemcitabine and cisplatin before chemotherapy,the serum levels of CA15-3,CA125 and NSE in the patients were decreased,and the difference was statistically significant( P <0.05),and the expression of mTOR and S6K1 protein and mRNA in breast cancer tissues were significantly decreased after chemotherapy,NF-κB protein content and mRNA expression increased significantly,it has significant statistical difference( P <0.05);The expression levels of p65 and Caspase 3 in patients were significantly increased,BCL-2 expression was significantly reduced,with significant statistical differences( P <0.05). Conclusion Gemcitabine combined with cisplatin has a certain therapeutic effect on breast cancer.And the mTOR/S6K1/NF-κB signaling pathway plays an important role in this process.