MAPK信号激活抑制三阴性乳腺癌细胞的迁移和侵袭

Activation of MAPK signaling is associated with migration and invasion of triple-negative breast cancer cells

背景与目的:三阴性乳腺癌具有高复发和转移风险,除了化疗,临床上无特定的靶向治疗。因此,研究三阴性乳腺癌复发转移机制对提高患者生存率具有重要意义,本研究旨在探讨丝裂原激活的蛋白激酶(MAPK)信号激活对三阴性乳腺癌细胞迁移和侵袭的影响。方法:首先用细胞划痕和细胞小室(Transwell)试验分析和比较肺高转移三阴性乳腺癌细胞系231-HM及其父代肺低转移细胞系231-p的体外迁移和侵袭性差异;然后用蛋白质印迹法(Western blot)检测转移相关蛋白和MAPK分子激活状态;最后用MAPK抑制剂处理231-p细胞,测定MAPK抑制情况下的细胞迁移、侵袭和相关蛋白变化。结果:与231-p细胞相比,231-HM细胞迁移和侵袭性明显增强;Western blot检测发现,231-HM细胞中促细胞迁移和侵袭蛋白Caveolin-1和β-catenin升高,MAPK通路相关蛋白P38、Erk1/2和MEK的磷酸化水平明显降低;用P38/MAPK磷酸化抑制剂(SB202190)处理231-p细胞后发现,其细胞迁移和侵袭性明显增强,Caveolin-1和β-catenin表达水平上升。结论:MAPK信号激活抑制三阴性乳腺癌的迁移和侵袭。

Background and purpose： Triple-negative breast cancer （TNBC） possesses high risk of relapse and metastasis. Clinically, there are no specific targeted-therapies to TNBC except chemotherapy. Therefore, studying the mechanism of relapse and metastasis has significance to improve the patients＇ survival rate. This experiment aimed to study the effect of MAPK activation on migration and invasion of triple-negative breast cancer cells. Methods： Difference of migration and invasion between lung-high metastasis breast cancer cell line 231-HM and its parental cell line 231-p were first examined by cell scratch and transwell; Then, metastasis-associated proteins and MAPK- associated molecules were detected by Western blot; Last, 231-p cells were treated with P38/MAPK inhibitor and used to determine cell migration, invasion, and metastasis-associated proteins thereafter. Results： Compared with the parental cell line 23 1-p, 231-HM cells displayed obviously higher ability of migration and invasion. With the increased expression of Caveolin-land β-catenin, the phosphorylation of MAPK-associated molecules including P38, Erk1/2, and MEK was highly decreased. Treatment of 231-p cells with low concentration （10 μmol/L） of the P38/MAPK inhibitor SB202190 increased the migration and invasion of 231-p cells, and the expression of Caveolin-1 and β-catenin. Conclusion： Activation of MAPK signaling inhibits the migration and invasion of triple-negative breast cancer.