干扰TGFβRⅠ增加乳腺癌细胞MDA-MB-231对化疗药物的敏感性

转化生长因子β(transforming growth factorβ,TGFβ)与其受体(transforming growth factorβreceptor,TGFβR)结合激活下游信号通路,在肿瘤的发生发展和转移中具有重要意义,且已有迹象表明该通路可能介导肿瘤的化疗耐受.本研究构建了干扰转化生长因子βⅠ型受体(transforming growth factor receptor typeⅠ,TGFβRⅠ)的重组质粒pRNAT-U6.1/TGFβRⅠ-sh1,发现其可在mRNA和蛋白质水平均显著下调TGFβRⅠ的表达,P0.01.后将该干扰质粒转染乳腺癌细胞MCF-7/5Fu、MCF-7、MDA-MB-231、MDA-MB-453,建立了稳定的乳腺癌TGFβRⅠ干扰模型;MTS法检测上述4种细胞模型对5-氟尿嘧啶(5-fluorouracil,5-FU)和紫杉醇(taxol,TAX)的敏感性.结果显示,MCF-7、MCF-7/5Fu和MDA-MB-453细胞在干扰TGFβRⅠ之后对5-FU和TAX敏感性并未发生改变;但是间质表型的MDA-MB-231细胞在干扰TGFβRⅠ之后对5-FU和TAX的敏感性显著增加.由此可见,干扰TGFβRⅠ的表达阻断TGFβ信号通路,进而显著增加间质型乳腺癌细胞对化疗药物的敏感性,这为临床乳腺癌治疗提供了一定的理论依据.

Knockdown of TGFβRⅠIncreases the Sensitivity of Human Breast Cancer Cell MDA-MB-231 Cells to Chemotherapy Drugs

The transforming growth factor β (TGFβ) signal pathway plays important roles in the development of tumor genesis and metastasis. However, the mechanism of TGFβ signal pathway mediating cancer chemotherapy resistance is unclear. Here,we knocked down the expression of TGFβ receptor (TGFβRI) by stably transfecting eukaryotic plasmid pRNAT-U6.1/shTGFβRI into breast cancer cell lines MCF-7, MCF-7/5Fu, MDA-MB-231 and MDA-MB-453. Then MTS assay was used to measure the sensitivity of these stable cell lines to 5-fluorouracil (5-Fu) and taxol（TAX). Our results showed that MCF-7, MCF-7/5Fu and MDA-MB-453 cell lines had no effect on sensitivity to 5-Fu and TAX with TGFβRI down-regulation, while MDA-MB-231 cell line with TGFβRI interfered was significantly sensitive to 5-Fu and TAX. These suggest that knockdown of TGFβRⅠblocks TGFβ signal pathway, and significantly increases the sensitivity of interstitial type breast cancer cell lines to chemotherapy drugs. This work provides a new theoretical basis for clinical breast cancer chemotherapy.