Preliminary Study Of Mir-155 Involved In Trastuzumab-resistance Of Breast Cancer

Background:Breast cancer is one of the most common cancer which threatens the health of women in the world and can lead them to death.Among them,HER-2 positive patients account for 20-30%.Trastuzumab is the most commonly used humanized monoclonal antibody in patients with HER-2 positive breast cancer,but the drug resistance problem has become the bottleneck of clinical treatment.The role of miR-155 is closely related with human tumors,but its relationship with trastuzumab resistance is not clear.Objective:To study the role of miR-155 in the resistance of trastuzumab in breast cancer.Methods:1.We selected HER2-positive SK-BR-3 cell line as the research object,and construct trastuzumab-resistant cell line SK-BR-3R by increasing concentration method.2.We detected miR-155 levels by real-time quantitative PCR in trastuzumab sensitive and resistance cell lines.3.We transfected miR-155 inhibitor or mimic by liposomes and measure cell viability and apoptosis by CCK8 and flow cytometry.4.Finally,we collected clinical specimens of trastuzumab-sensitive and resistant patients and detected the levels of miR-155 in the specimens.Result:1.We successfully established trastuzumab-resistant cell line SK-BR-3R.2.The expression of miR-155 was significantly up-regulated in trastuzumab-resistant breast cancer cells.3.Silencing of miR-155 expression in SK-BR-3R cells could increase the sensitivity of trastuzumab-resistant cells,while SK-BR-3 cells overexpressing miR-155 were less sensitive to trastuzumab.4.Furthermore,we found that miR-155 was increased in trastuzumab-resistant tissuss.Conclusion:We established a trastuzumab-resistant HER2-positive breast cancer cell line and found that miR-155 was up-regulated in trastuzumab-resistant breast cancer cells for the first time.Moreover,miR-155 can affect the sensitivity of breast cancer cells to trastuzumab and it is expected to be a new target for solving the resistance of trastuzumab in breast cancer.