In Vitro And In Vivo Study Of Non-homologous Terminal Junction Activity On Cisplatin Sensitization In Triple Negative Breast Cancer

Objective:In this study,we observed whether SCR7 sensitizes cisplatin in the treatment of triple negative breast cancer in vitro and in vivo,and explored whether SCR7 also affects the repair pathways of XRCC1 and PARP1,and explored the mechanism of SCR7 sensitizing cisplatin,so as to provide theoretical reference for the clinical treatment of triple negative breast cancer.Methods:TNBC mda-mb-231 cells were cultured in vitro.They were divided into negative control group,DDP Group,SCR7 group and SCR7 + DDP Group.CCK-8 method was used to detect cell activity and calculate the inhibition rate of cell proliferation.The drug-drug Interaction Coefficient(CDI)was used to evaluate the interaction between SCR7 and DDP.TNBC MOUSE MODEL was established by TNBC MDA-MB-231 cells.The nude mice were randomly divided into model group,CISPLATIN group and SCR7 + DDP group.Weight and tumor size were recorded.For 24 days.Then the tumor inhibitory rate was calculated after removal and weighing of breast tumor,the histocytomorphology of the tumor was observed using hematoxylin-eosin(HE)staining The apoptosis of tumor cells was detected by TUNEL method,and the expressions of XRCC1 and PARP 1 proteins were detected by Western blot.Results:In vitro cell experiment:(1)After gradually increasing the incubation time,it can be found that cisplatin +SCR7 group,SCR7 and cisplatin have significantly higher inhibition rate.In addition,the inhibition rate of SCR7 + cisplatin group is significantly higher than that of cisplatin group and SCR7 group within the same time period(P < 0.05).(2)The results shows that CDI of DDP and SCR7 was 0.75,which has significant cooperativity.In vivo animal experiments:(1)With the feeding time increased,it is shown that all the weight increased.No difference can be observed in the weight of cisplatin + SCR 7 group as compared with the cisplatin group(P > 0.05).(2)If feeding time was increased further,the tumor volume of mice in each group increased.The tumor volume of SCR7 + DDP group was the smallest and significantly smaller than that of the other groups(P < 0.05),model group has the highest tumor volume(P < 0.05).(3)For both cisplatin + SCR7 and cisplatin groups,the tumor cells degenerated in varying degrees,nuclear fragments and the density decreased.The degeneration of tumor cells in SCR7 + cisplatin group was the most significant.(4)Apoptosis in breast cancer tissues: Red apoptotic cells were almost invisible in the model group,and some red apoptotic cells were found in DDP group.A large number of red apoptotic cells were observed in SCR7 + DDP group.(5)The protein expressions of XRCC1 and PARP1 in SCR7 + cisplatin group were significantly lower than those in other groups(P < 0.05).Conclusion: SCR7 has a sensitization effect on cisplatin chemotherapy of triple-negative breast cancer in vitro and in vivo.It strongly strengthen the cisplatin-induced apoptosis of MDA-MB-231 cells,and then inhibit the expression of XRCC1/PARP1 protein.