Study on the sensitizing effect of SCR7 on cisplatin chemotherapy in triple-negative breast cancer

Abstract:

Objective To investigate the sensitizing effect of SCR7 on cisplatin chemotherapy in triple-negative breast cancer（TNBC）.Methods MDA-MB-231 cells of TNBC were selected and divided into blank control group，10 μmol/L cisplatin control group and combined group（10 μmol/L cisplatin + 10，20 and 40 μmol/L SCR7）. CCK-8 method was used to detect cell activity and calculate cell proliferation inhibition rate. A TNBC mice model was constructed by using TNBC MDA-MB-231 cells. The nude mice were randomly divided into control group，SCR7 group，cisplatin group and SCR7+cisplatin group. After 24 days of feeding，the changes of mass and tumor volume of tumor-bearing mice in all groups were observed and compared，and the tumor inhibition rate was calculated. Morphological changes of tumor cells were observed by hematoxylin - eosin（HE） staining. The apoptosis of tumor cells was detected by in situ end labeling（TUNEL） method，and the expressions of X-ray repair cross complementing 1（XRCC1） and poly（ADP-ribose） polymerase 1（PARP1） proteins were detected by Western blot.Results The cell proliferation inhibition rate in the combined group was higher than that in the control group（P<0.05），and it wasgradually increased with the increase of SCR7 concentration（P<0.05）. Animal experiments in vivo found：compared with the control group，the tumor volume and tumor weight of breast cancer in SCR7 group，cisplatin group and SCR7+cisplatin group decreased（P<0.05），and the tumor inhibition rates were 32%，40% and 81%，respectively. The SCR7+cisplatin group showed a more significant reduction than SCR7 group and cisplatin group（P<0.05），but there was no significant difference in mouse body weight compared to the cisplatin group（P>0.05）. The tumor tissues in the intervention groups showed obvious morphological changes by HE staining，among which the tumor cells in the SCR7+cisplatin group showed the most obvious degenerative changes. TUNEL staining showed that the tumor cells in the SCR7+cisplatin group had the most serious apoptosis，and a large number of red apoptotic cells were seened. Western blotting showed that the protein expressions of XRCC1 and PARP1 in SCR7+cisplatin group were significantly lower than those in other groups，and the differences were statistically significant（P<0.05）.Conclusion SCR7 has sensitizing effect on cisplatin chemotherapy for TNBC in vivo and in vitro.