不同化疗药物对三阴乳腺癌亚型的作用效果研究

Study on the effects of different chemotherapeutic drugs on different subtypes of triple negative breast cancer

目的探究不同化疗药物对不同三阴乳腺癌(Triple negative breast cancer,TNBC)亚型的作用效果。方法培养人三阴乳腺癌MDA-MB-231、MDA-MB-468、SKBR-3、HCC1937细胞株,MTT法测定各株细胞在不同化疗药物(表柔比星、紫杉醇、5氟尿嘧啶、顺铂、环磷酰胺)作用下的增殖抑制,经流式细胞仪分析各细胞株中ALDHhiCD44+CD24-/low干细胞的含量以及在不同药物作用后其含量的变化,Western印迹检测不同细胞株内ERCC1、TOPOIIα、TS、β3-tubulin等耐药相关蛋白的表达情况。结果体外实验中,不同三阴乳腺癌亚型细胞株对不同的化疗药物反应性不同,细胞株中ALDHhiCD44+CD24-/low细胞含量不同,耐药相关蛋白表达存在差异。结论不同化疗药物对三阴乳腺癌亚型的作用效果存在差异,这种差异体现在干细胞含量、蛋白表达水平等多个层面上。

Objective To explore the effects of different chemotherapeutic drugs on different subtypes of triple negative breast cancer （TNBC） . Methods Human TNBC MDA-MB-231, MDA-MB-468, SKBR-3, and HCC1937 cell lines were cultured. MTT assay was used to detect the inhibiting effects of different chemotherapeutic drugs （ epirubicin, paclitaxel, 5-fluorouraeil, cisplatin, and cyclophosphamide ） on proliferation of different cell lines. Flow cytometry was used to analyze the contents of ALDH^hiCD144^＋CD24^-/low breast cancer stem cells in different cell lines and the changes of contents after treated by different chemotherapeutic drugs. Western blot was used to detect the expressions of drug-resistant related proteins （ERCC1, TOPOIIα, TS, and β3-tubulin） in different ceil lines. Results In in vitro experiment, the responses of different TNBC cell lines to different chemotherapeutic drugs varied, the contents of ALDH^hiCD144^＋CD24^-/low cells in different cell lines were different, there were differences in the expressions of drug-resistant related proteins. Conclusion The effects of different chemotherapeutic drugs on different subtypes of TNBC are different, which are reflected in multiple levels, such as the content of stem cells and expression levels of proteins.