扶正中药逆转TLR4过表达乳腺癌紫杉醇耐药的机制

Mechanism of Chinese medicine Fuzheng in reversing paclitaxel resistance in TLR4 over-expressed breast cancer

目的:探讨扶正中药联合紫杉醇(PTX)逆转TLR4过表达乳腺癌细胞株MDA-MB-231对PTX的耐药及对TLR4/NF-κB信号通路的影响。方法:MTT实验检测扶正中药、PTX及两药联用对乳腺癌细胞株T47D及MDAMB-231的增殖抑制作用;流式细胞技术检测细胞凋亡率,Western blot检测细胞凋亡相关蛋白及TLR4/NF-κB信号通路相关蛋白的表达。结果:扶正中药与PTX在处理MDA-MB-231细胞株时有协同作用,可诱导MDAMB-231细胞株细胞凋亡增加(P<0.05),使TLR4/NF-κB信号通路相关蛋白TLR4、p-lκBα、NF-κB表达减少(P<0.05)。结论:MDA-MB-231细胞株中,扶正中药可以通过抑制TLR4/NF-κB信号通路增加细胞凋亡,从而增加PTX对MDA-MB-231乳腺癌细胞株的增殖抑制作用,逆转乳腺癌对PTX的耐药。

Objective:To investigate the mechanism of Fuzheng Chinese medicine combined with paclitaxel against TLR4 over-expressing breast cancer,and to confirm the sensitization effect of traditional Chinese medicine combined with chemotherapy for TLR4 over-expressed breast cancer MDA-MB-231 so as to select specific tumor phenotype for combination of traditional Chinese and western medicine.The target provides drug intervention to provide basic data.Methods:MTT assay was used to detect the proliferation inhibition effect of Fuzheng Chinese medicine,paclitaxel and two drugs on breast cancer cell lines T47D and MDA-MB-231.The apoptosis rate was detected by flow cytometry.Expression of the apoptosis related protein and TLR4/NF-kB signaling pathway-associated proteins was detected by Western blotting technology.Results:Fuzheng Chinese medicine and paclitaxel had synergistic effect in the treatment of MDA-MB-231 cell line;Fuzheng Chinese medicine assisted paclitaxel to induce apoptosis of MDA-MB-231 cell line(P<0.05);combined with Chinese medicine and paclitaxel,MDA-MB-231 Cell line TLR4/NF-kB signaling pathway was inhibited(P<0.05).Conclusion:In MDA-MB-231 cell line,Fuzheng Chinese medicine can increase cell apoptosis by inhibiting TLR4/NF-kB signaling pathway,thereby increasing the cell proliferation inhibition effect of paclitaxel on MDA-MB-231 breast cancer cell line and reversing paclitaxel-resistance in breast cancer.