The Correlation Between The Expression Of Transmembrane TNF-α And Chemoresistance In Invasive Ductal Breast Cancer

Objective: To investigate the expression of transmembrane TNF-α (tmTNF-α) and thechemoresistance of invasive ductal breast cancer, we explore the relation between theexpression of tmTNF-α and chemoresistance in invasive ductal breast cancer. Toinvestigate the effect of tmTNF-α-shRNA on the expression of tmTNF-α andchemotherapeutic sensitivity of invasive ductal breast cancer to adriamycin.Method:20cases of primary invasive ductal breast cancer were tasted with ATP-TCAassay to evaluate their chemoresistance. The chemotherapy drugs included adriamycin(Adr) and docetaxel(Doc). The expression of tmTNF-α was examined with immune-histochemical assay. The tmTNF-α-shRNA plasmids were transfected into humanprimary invasive ductal breast cancer cells with a high expression of tmTNF-α by Lipo-fectamine2000, the expression of tmTNF-α was detected by reverse transcription-PCR(RT-PCR), The cellular sensitivity to chemotherapy was detected by ATP-TCA.Result: The percentage of drug resistance of adriamycin and docetaxel were55.00%and57.89%, respectively. There were5cases resisting both medications, while therewere2cases sensitizing both medications. The expression of tmTNF-α was positive in the tumor tissues in all the20patients, but negative in normal breast tissues andparacacinomatous tissues. The expression of tmTNF-α was not associated with thestatus of ER, PR, HER2and lymph node metastasis(P＞0.05). The expression oftmTNF-α had a parallel relationship with the degrees of chemoresistance in adriamycin(P＜0.05), but was not associated with docetaxel(P＞0.05). Results of RT-PCRshowed that the expression of tmTNF-α mRNAs was reduced significantly aftertransfecting tmTNF-α-shRNA24h. The chemosensitivity assays indicated that thetransfected cells showed an enhanced sensitivity to adr in transfected human primaryinvasive ductal breast cancer cells.Conclusions：A higher positive expression of tmTNF-α is present in invasive ductalbreast cancer patients, and the expression of tmTNF-α participates in the chemo-resistance in primary invasive breast cancer patients. The results suggest that theshRNA can reverse the tmTNF-α-caused chemoresistance of human invasive ductalbreast cancer cells. RNA interference (RNAi) may provide a new effective therapeutictechnology for the treatment of human invasive ductal breast cancer.