Mannose Inhibits Proliferation Of Breast Cancer Cells And Increases Chemosensitivity Of Epirubicin

Objective: To detect the expression of mannose phosphate isomerase in breast cancer cell lines and its relationship with mannose inhibiting tumor cell growth.To explore the effect of mannose on the biological activity of breast cancer cells and its mechanism.To explore the effect of mannose combined with chemotherapy drug epirubicin on the biological activity of breast cancer cells.To investigate the effect of mannose and mannose combined chemotherapy drug epirubicin on the biological activity of breast cancer cells under hypoxia.Methods: Breast cancer cell lines T-47 D and MCF-7 were selected.MTT colorimetry was used to determine the effect of mannose and mannose combined with epirubicin on the growth activity of breast cancer cells.Scratch test was used to detect the effect of mannose on the migration ability of breast cancer cells.The expression changes of Phosphomannose Isomerase(PMI),a key protein involved in glucose metabolism by mannose in breast cancer cells,and apoptosis-related proteins Caspase 3,Caspase 8,Bax and Bcl-2 were determined by Western blot.Res?lts: Under normal aerobic conditions,the proliferation rate of mannose group of T-47 D cells was significantly lower than that of control group and the difference was statistically significant(F=124.203,P<0.01).Compared with the control group,the mannose group has the shortest migration distance of T-47 D cells and the glucose group has the longest migration distance.And the difference is statistically significant(F= 251.656,P<0.01).Mannose increased the chemosensitivity of T-47 D cells to epirubicin to 1.34 and 0.08 times(F=1150.190,P<0.01).Mannose still inhibited T-47 D cells under hypoxia(F=17.914,P<0.01),and increased the chemosensitivity of T-47 D cells to epirubicin(F=45.375,P<0.01).Under normal aerobic conditions,mannose had no obvious inhibitory effect on MCF-7 cells(F=86.553,P>0.01).Compared with epirubicin monotherapy group,mannose combined with epirubicin group had no significant difference in cell proliferation rate(F=15.877,P>0.01).However,the proliferation rate of mannose group of MCF-7 cells was significantly lower than that of control group under hypoxia condition and the difference was statistically significant(F=9.501,P<0.01).Mannose increased the sensitivity of MCF-7 cells to epirubicin to 1.93 and 0.02 times under hypoxia(F=107.931,P<0.01).The expression of PMI in breast cancer cell lines is significantly different(F=392.680,P<0.01).The expression of PMI in T-47 D is relatively low and the difference is statistically significant(LSD-t=32.856,P<0.01).The expression of PMI in MCF-7 cells is relatively high and the difference is statistically significant(LSD-t=25.017,P<0.01).Compared with the control group,the expression of apoptosis-related proteins Caspase3? Caspase8?Bax and Bcl-2 in each experimental group had no significant difference(F=6.534,P>0.01).Conclusion: Mannose can inhibit the growth and proliferation of breast cancer cells and increase the sensitivity of breast cancer cells to the chemotherapeutic drug epirubicin.Breast cancer cell lines with relatively low PMI expression are more susceptible to mannose.In cell lines with relatively high PMI expression,mannose can increase its sensitivity to mannose under hypoxia conditions,which shows that mannose obviously inhibits its proliferation and increases its sensitivity to epirubicin.However,as cell lines with relatively low PMI expression,anoxic conditions did not increase their susceptibility to mannose.The sensitivity of breast cancer cells to mannose is closely related to PMI expression level.The inhibitory effect of mannose on the growth and proliferation of breast cancer cells has nothing to do with the common mitochondrial apoptosis pathway.