Experiment Study On The Effects Of Trastuzumab Combined With Fulvestrant In HR+/HER2+ Breast Cancer

Objective To investigate the effects of trastuzumab combined with fulvestrant in HR+/HER2+breast cancer and research the related mechanisms.Method Inhibition of HR+/HER2+human breast cancer cell proliferation at different concentrations of trastuzumab and fulvestrant as single agents or a combinatioin was observed using the WST-1 assay.Flow cytometry?FCM?was used to assess the cell apoptosis rates by Annexin-V/PI assay and the cell cycle by PI assay.Besides,the levels of proteins p-Akt and p-Erk expressed in cells were detected by immunoblot assay.In addition,tumor growth inhibition and p-MED1 expressed in tumor tissues were inspected using breast cancer xenograft models.Result The cell proliferation was increasingly inhibited by trastuzumab or fulvestrant or both when the drug concentration added,with a CI<1 and a DRI>1 in both cell lines.Only BT-474 cell apoptosis rate was distinctly increased when fulvestrant affected as a single agent or a combination with trastuzumab?P<0.05?,but no statistical difference was defected between them?P>0.05?.Besides,no effects were observed on ZR-75-1 cell apoptosis rate in whatever group?P>0.05?.Cell accumulation in the G₁ phase of cell cycle was inspected in all treatment groups?P<0.05?,and the combination of trastuzumab and fulvestrant inhibited the function of fulvestrant raising the level of proteins p-Akt and p-Erk.Using BALB/c athymic ZR-75-1 or BT-474 in vivo xenograft models,the combination showed stronger inhibition of tumor growth?P<0.05?and greater decrease on p-MED1 expressed in tumor issues compared witheither single agent.Conclusion The combination of trastuzumab and fulvestrant is demonstrated to generate synergistic effects on both HR+/HER2+cell lines ZR-75-1 and BT-474,and at the same time decrease each drug's doses,possibly reducing the occurrence of both drugs'side effects.Besides,tumor growth is highly inhibited by the combination,providing a theoretical basis for the combination treatment in clinical application.