Inhibitory Effect Of Apatinib Combined With Vinorelbine On Breast Cancer Cells Growth In Vitro And In Vivo And Its Mechanism

Objective:The experiments were conducted to investigate the inhibitory effect of apatinib combined with vinorelbine on proliferation of breast cancer cells in vitro and in vivo,and the mechanism was initially explored.Methods:1.4T1 mouse breast cancer cells were cultured in vitro.MTT assay was used to detect the inhibitory effect of apatinib monotherapy,vinorelbine monotherapy,apatinib combined with vinorelbine on breast cancer cells,and the growth curve was drawn.2.Detection of apoptosis: After cultured mouse breast cancer 4T1 cells,flow cytometry was used to detect the effects of apatinib monotherapy,vinorelbine monotherapy,apatinib combined with vinorelbine on apoptosis.3.The mouse 4T1 breast cancer model was constructed.The mice were divided into blank group,apatinib group,vinorelbine group and combination group.The tumor length,width and mouse body weight were measured every 3 days.Tumor volume(mm3)= length(mm)× width(mm)× width(mm)/ 2 formula calculates the tumor size,calculates the tumor inhibition rate,and plots the tumor growth curve.Three weeks after the administration,the mice were sacrificed by cervical dislocation,and the mouse mammary tumors were taken out and immersed in a 10% formalin fixative for immunohistochemical detection;lung tissues were taken out and lung metastasis was counted.4.Immunohistochemistry was used to detect the expression levels of VEGF,VEGFR2,CD31 and Ki-67 in mouse mammary gland.Results:1.In vitro cultured mouse 4T1 cells,combined with single drug and blank control group,the proliferation inhibition effect was significantly enhanced,the difference was statistically significant;the apoptosis induced by the combined group was significantly higher than the single drug group.2.In vivo experiments show that apatinib combined with chemotherapy can significantly inhibit tumor growth and reduce the number of lung metastases.The results of immunohistochemistry showed that the expression of VEGF,VEGFR2,CD31 and Ki-67 in serum and tumor tissues of the combined group showed that apatinib combined with vinorelbine could decrease the expression of VEGF,VEGFR2,microvessel density and enhance tumor suppression effect.Conclusion:In vitro and in vivo studies have shown that the effect of apatinib combined with chemotherapy on the malignant behavior of breast cancer may be related to enhanced inhibition of VEGF/VEGFR2 expression and decreased microvascular density of tumor tissue.