Study Of RBBP4 As A New Target For The Treatment Of Breast Cancer

Objective Breast cancer is one of the major diseases that have long endangered harm the lives and health of women around the world.According to the latest statistics from the American Cancer Society,breast cancer has surpassed lung cancer and become the number one malignancy in the world.The treatment of breast cancer is complicated by its multiple strains and the differences in malignancy,sensitivity to treatment and prognosis among the different strains.In recent years,despite the encouraging results of new combination therapies and molecular targeted therapies for breast cancer,there are still significant shortcomings in the existing therapies,and the number of breast cancer incidence and death continues to increase year by year.The search for new anti-breast cancer targets and therapies remains the key in the current breast cancer treatment field.Our previous study found that Retinoblastoma-binding protein 4(RBBP4)is overexpressed in human lung,gastric,colorectal and cervical cancers,and this abnormally high expression plays a crucial role in the proliferation of these tumors.Accordingly,what about the expression of RBBP4 in human breast cancer cells?Could RBBP4 be a new target for breast cancer treatment?Our study has been carried out to investigate them.Methods The expression of RBBP4 in human breast cancer and its paraneoplastic tissues was detected by immunohistochemistry;The expression of protein in human normal breast cells and breast cancer cells was detected by Western blot;The expression of the target gene was inhibited by RNA interference technique;The proliferation of cells was detected by MTT;Human breast cancer cell lines overexpressing the target gene were constructed with lentiviral vectors,and the expression of the target gene was observed by immunofluorescence;The expression of the lentiviral vector in the cells was observed by immunofluorescence.Results Among 68 cases of human breast cancer tissue samples,44 cases(64.71%)were moderately-strongly positive for RBBP4 expression,while only 21 cases(30.88%)of the paired paraneoplastic tissues were moderately-strongly positive;There is a significant difference between them(P<0.001).MTT results showed that downregulation of RBBP4 significantly decreased the proliferation of human breast cancer cell lines MCF-7,T-47D,MDA-MB-231,MDA-MB-468 and BT-549.MCF-7 and MDA-MB-231 with overexpression of RBBP4 were able to significantly antagonize the inhibitory effect of down-regulation of RBBP4 on cell proliferation.Downregulation of RBBP4 significantly increased the inhibitory effect of paclitaxel and cisplatin on human breast cancer cell lines.The results of mechanistic studies showed that the expression of Cyclin D1 and CDC25C was significantly inhibited in MCF-7,T-47D,MDA-MB-231,MDA-MB-468 and BT-549 cells after down-regulation of RBBP4.Human breast cancer cell lines MCF-7 with overexpression of Cyclin D1 and CDC25C,MDA-MB-231 and MDA-MB-468 with overexpression of CDC25C were able to reverse the inhibitory effect of down-regulation of RBBP4 on human breast cancer cell lines.Conclusion 1.RBBP4 was significantly overexpressed in human breast cancer cell lines;2.Down-regulation of RBBP4 inhibited the proliferation of human breast cancer cell lines;3.Down-regulation of RBBP4 increased the sensitivity of human breast cancer cell lines to the chemotherapeutic drugs paclitaxel and cisplatin;4.Downregulation of RBBP4 produced an inhibitory effect on the proliferation of human breast cancer cell lines mainly by inhibiting the expression of Cyclin D1 and CDC25C;5.RBBP4 is expected to be a new target for the treatment of human breast cancer.