FGF2通过活化Akt-mTOR信号促进乳腺癌细胞化疗耐受

发布时间：2019-03-16 14:22

【摘要】：目的:探讨成纤维细胞生长因子FGF2在介导乳腺癌化疗耐受中的作用及机制。方法:用不同信号通路抑制剂处理两株乳腺癌耐药细胞系MCF-7/5-Fu和T47D/5-Fu,MTS实验检测药物敏感性,Hoechst染色检测细胞凋亡,Western blot检测蛋白活性变化,ELISA检测FGF2蛋白含量。结果:Akt抑制剂、m TOR抑制剂和FGFR抑制剂能明显逆转耐药细胞对5-Fu和Paclitaxel的耐药性,而ERK1/2抑制剂对耐药细胞的化疗敏感性无明显影响。耐药细胞中p-Akt、和p-S6K(即m TOR活性)水平高于亲本细胞,耐药细胞中FGF2 m RNA和培养上清中FGF2蛋白含量高于相应的亲本敏感细胞。FGF2重组蛋白可增加亲本细胞对5-Fu和Paclitaxel的耐药性,同时活化Akt-m TOR信号通路。结论:FGF2-FGFR-Akt-m TOR信号活化促进乳腺癌化疗耐受。
[Abstract]:Objective: to investigate the role and mechanism of fibroblast growth factor (FGF2) in mediating chemotherapy tolerance of breast cancer. Methods: two drug-resistant breast cancer cell lines, MCF-7/5-Fu and T47D-5-Fu, were treated with different signal pathway inhibitors. The drug sensitivity was detected by Hoechst assay, and the changes of protein activity were detected by, Western blot staining. The content of FGF2 protein was detected by ELISA. Results: Akt inhibitor, m TOR inhibitor and FGFR inhibitor could significantly reverse the drug resistance of resistant cells to 5-Fu and Paclitaxel, but ERK1/2 inhibitor had no obvious effect on chemosensitivity of drug resistant cells. The levels of pTAkt and p-S6K (m-TOR activity) in drug-resistant cells were higher than those in parental cells. The contents of FGF2 m RNA in drug resistant cells and FGF2 protein in culture supernatant were higher than those in parental sensitive cells. FGF2 recombinant protein increased the resistance of parental cells to 5-Fu and Paclitaxel, and activated the Akt-m TOR signaling pathway at the same time. Conclusion: activation of FGF2-FGFR-Akt-m TOR signal promotes chemotherapy tolerance of breast cancer.
【作者单位】：广州医科大学附属肿瘤医院;
【基金】：国家自然科学基金项目(编号:81402196) 广州市属高校科研项目(编号:1201430498) 广州市科信局科学研究专项项目(编号:2014J4100061)
【分类号】：R737.9

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