Inhibition Effect And Mechanism Of S~4TdR/UVA On Viability Of Breast Cancer Cell MCF-7

Breast cancer is a highly heterogeneous malignant tumor disease affected by estrogen.It has become one of the greatest threats to the health of women,with a yearly increasing trend in female incidence rate around the world.Currently,the common treatments for breast cancer have many defects,such as large wound surface,poor targeting,obvious side effects,poor prognosis and easy to relapse,which often lead to the failure of best therapeutic effect.Some studies have shown' that S4TdR has the characteristics of low toxicity and weak mutagenicity.When combined with UVA,it can selectively destroy the DNA of some superficial cancer cells and induce apoptosis.Whether this promising new photodynamic therapy can be used in the treatment of breast cancer has not been reported.In this study,the in vitro effects of S4TdR/UVA on proliferation and cell cycle in human breast cancer cell MCF-7 have been obseved to study the feasibility of this new therapy on the treatment of breast cancer.Genes and proteins in two p53-related pathways,P53-Mdm2-P21 and P53-Bax/Bcl-2-Caspase 3,were quantitative analyzed to explore the molecular mechanism of S4TdR/UVA therapeutic effects on MCF-7.The cell viability assay showed that both 10-5 and 10-6M S4TdR combined with 5KJ/m2 UVA could significantly inhibit the proliferation of MCF-7 cells induced by E2,and the inhibition effect of 10-6M S4TdR was more obvious.The detection of cell cycle further proved that 10-6M S4TdR/UVA could affect the cell replication process by increasing the G1 phase cell number and decreasing the S phase cell number of MCF-7 cells,which in turn leads to the inhibition of cell proliferation.The quantitative analysis of apoptosis related molecules showed that 10'6M S4TdR/UVA could increase the expression of p53,decrease the expression of p53 negative feedback regulator,MDM2,and thus activate the downstream gene p21,which form the cell cycle checkpoints with p53 inducing cell cycle arrest.On the other hand,p53 could activate downstream gene Bax and inhibit bcl-2,antagonist of Bax.By increasing the expression ratio of Bax/Bcl-2,p53 could activate caspase-3 and induce apoptosis.Our study demonstrated the therapeutic effect of S4TdR/UVA in breast cancer cell,provided basic data for the development of highly targeted antitumor photosensitizers and revealed the molecular mechanism of S4TdR/UVA therapeutic effect on breast cancer cell MCF-7.