摘要
背景与目的:统计表明90%以上肿瘤患者的死亡与肿瘤耐药相关,而在乳腺癌中常见PI3K/Akt/mTOR信号通路的异常激活,以此通路为靶点的药物已成为乳腺癌治疗的研究热点。本研究主要分析C族趋化因子配基1(C chemokine ligand 1,XCL1)对乳腺癌耐药细胞增殖的影响及其产生机制。方法:建立吉西他滨耐药性人乳腺癌细胞系MDA-MB-231/Gem。采用CCK8检测MDA-MB-231和MDA-MB-231/Gem的增殖能力,RT-PCR、ELISA检测2株细胞株XCL1表达差异,Western blot检测mTOR的表达。结果:与MDA-MB-231相比,MDA-MB-231/Gem的增殖能力增强,XCL1在耐药细胞株表达增强。mTOR在耐药细胞株表达水平及磷酸化水平增强。在MDAMB-231中加入外源性XCL1 24 h后,细胞增殖能力增强。而在MDA-MB-231/Gem中加入抗XCL1抗体后,细胞增殖能力降低。mTOR抑制剂处理MDA-MB-231/Gem后,细胞增殖能力降低,XCL1产生减少。结论:趋化因子XCL1的分泌可促进乳腺癌耐药细胞的增殖并由mTOR信号通路介导产生。
Background and purpose： More than 90% of cancer patients are incurable because of drug resistance. Activation of PI3K/Akt/mTOR signaling pathway in breast cancer, as a target for chemotherapy drugs has become a hot topic of breast cancer treatment. This study aimed to investigate the effect and mechanism of XCL1 on the proliferation of drug-resistant breast cancer cell, whether is related with the mTOR signaling pathway. Methods：Established gemcitabine-resistant breast cancer cell lines （MDA-MB-231/Gem）. CCK8 to detect the proliferation of MDA-MB-231 and MDA-MB-231/Gem, RT-PCR and ELISA to determine the XCL1 expression level of the two cell lines, Western blot to detect the expression of mTOR. Results：Compared with MDA-MB-231, MDA-MB-231/Gem showed an enhanced proliferative capacity. The expression of XCL1 was increased in the resistant cell lines. Both of protein level and phosphorylation level of mTOR increased in drug-resistant cell lines. The MDA-MB-231 added exogenous XCL1 for 24 h, showed an enhanced cell proliferation. Adding anti-XCL1 antibodies in MDA-MB-231/Gem could reduce cell proliferation and treating MDA-MB-231/Gem with the mTOR inhibitor could also reduce cell proliferation, as well as the XCL1 expression level. Conclusion：XCL1 promotes the proliferation of drug-resistant breast cancer cells mediated by activation of the mTOR pathway.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2014年第10期770-776,共7页
China Oncology
基金
国家自然科学基金资助项目(No:81172506)
上海市乳腺肿瘤重点实验室资助项目(No:12DZ2260100)
