三阴性乳腺癌细胞中上皮间质转化与EGFR单抗治疗效果的相关性
Correlation Between Epithelial-mesenchymal Transition and Sensitivity to EGFR Targeted Monoclonal Antibody in Triple Negative Breast Cancer Cells
-
摘要: 目的 研究三阴性乳腺癌（triple negative breast cancer, TNBC）细胞株的上皮间质转化（epithelial-mesenchymal transition, EMT）水平与西妥昔单抗药敏性的相关性。方法 （1）运用免疫印记法比较TNBC细胞株中EGFR、波形蛋白（vimentin）以及E钙黏蛋白（E-cadherin）的表达水平。（2）通过CCK8试剂比较不同细胞株对西妥昔单抗的敏感度。（3）采用Ⅰ型组蛋白去乙酰化酶抑制剂恩替诺特（ENT）逆转MDA-MB231的EMT。（4）观察ENT联合西妥昔单抗对MDA-MB231细胞活性的抑制作用。结果 （1）MDA-MB468细胞中E-cadherin的表达水平明显高于MDA-MB436及MDAMB231细胞；vimentin的表达水平明显低于MDA-MB436及MDA-MB231。（2）MDA-MB468对西妥昔单抗的敏感度明显高于MDA-MB231及MDA-MB436。（3）MDA-MB231的EMT能被Ⅰ型组蛋白去乙酰化酶抑制剂ENT逆转。（4）ENT单药显著抑制MDA-MB231细胞的活性，ENT联合西妥昔单抗较ENT单药对细胞生长的抑制作用更加显著。结论 TNBC细胞中，EMT与EGFR单克隆抗体西妥昔单抗的疗效可能相关。联合Ⅰ型组蛋白去乙酰化酶抑制剂ENT以及西妥昔单抗治疗可能是治疗TNBC的新方法。Abstract: Objective To observe the relationship between epithelial-mesenchymal transition (EMT) and the sensitivity of triple negative breast cancer (TNBC) cells to EGFR targeted monoclonal antibody. Methods (1) We compared the expression level of EGFR, vimentin and E-cadherin in TNBC cells by immunoblotting. (2) We observed the sensitivity of individual cell line to cetuximab by CCK8 kit. (3) We managed to reverse the EMT of MDA-MB231 with a type I histone deacetylase inhibitor Entinostat (ENT). (4) We observed the suppression effect of the combination of ENT and cetuximab on the viability of MDA-MB231 cells. Results (1) The expression level of E-cadherin was significantly higher and the expression level of vimentin was significantly lower in MDA-MB468 cells than in MDA-MB436 and MDA-MB231 cells. (2) MDA-MB468 cells were more sensitive to cetuximab than MDA-MB231 and MDA-MB436 cells. (3) ENT could reverse the EMT of MDA-MB231 cells. (4) The viability of MDA-MB231 cells was suppressed significantly by ENT treatment while the effect of the combination of ENT and cetuximab was more profound. Conclusion EMT might predict the sensitivity of TNBC cells to cetuximab. The combination of ENT and cetuximab might be the new approach in treating TNBC.
下载:
