Correlation Between AIB1 And Cervical Cancer CRT Sensitivity And Its Association With Clinical Significance

Background AIB1,also known as SRC-3,a member of the p160 nuclear receptor coactivator family,was found to have been amplified in breast cancer in 1997 and is considered to be an important oncogene in breast cancer.SRC-3 was originally identified as a transcriptional coactivator of nuclear receptors,such as the estrogen receptor(ER).AIB1 is involved in the proliferation of hormone-dependent cancers,and its elevated levels are associated with poor clinical prognosis.AIB1 has also been found to be associated with a variety of cancers,including gastric cancer,olorectal cancer and hepatocarcinoma,which mediate a variety of non-hormone-dependent tumor-associated signaling pathways.But there is still a lack of research in cervical cancer.This study combines AIB1 and cervical cancer radiotherapy and chemotherapy to understand the effect of AIB1 on the chemoradiotherapy of cervical cancer.The aim is to find suitable biomarkers for assessing the prognosis of cervical cancer,which may provide a potential target for the treatment of cervical cancer.Objective To investigate the effect of AIB1(amplified in breast cancer 1)on the chemoradiotherapy of cervical cancer.Methods AIB1 was stably knocked out in two cervical cancer cell lines(Si Ha and Ca Ski)by lentiviral-mediated RNA interference method,cervical cancer cell Si Ha-sh AIB1 was set as experimental group,and Si Ha-shluc was used as control group.The number of cell colonies was counted by plate cloning experiments,and the linear quadratic model curve(LQ)curve was used for fitting.The survival fraction of cervical cancer cells Si Ha was calculated by different doses,and the radiosensitization ratio(SER)was obtained.Apoptosis of cells was detected by flow cytometry with Annexin V-FITC/PI double staining.The expression levels of cleaved-CPAR and Cleaved-Caspase3 were detected by Western blotting.Results In Si Ha cells,knockdown of AIB1 caused a decrease in cell survival fraction(SF),SF2 of Si Ha-shluc and Si Ha-sh AIB1 were: 0.495 and 0.392 respectively,and radiosensitization ratio(SER)= 1.264 after AIB1 knockout.In Si Ha and Ca Ski cells,interference with AIB1 expression caused a decrease in IC50 value of 5-Fu(P<0.05).The percentage of apoptotic cells in flow cytometry and the expression levels of the Cleaved-PARP and Cleaved-casepase3 in western blot increased.Conclusion The decrease of AIB1 expression is associated with increased apoptosis after radiotherapy for cervical cancer.The knockdown of AIB1 could reduce the IC50 value of cytotoxic drugs,indicating that high expression of AIB1 can cause chemoradiotherapy resistance of cervical cancer,and AIB1 is a potential target to improve the sensitivity of chemoradiotherapy for cervical cancer.