EP221/#1446  The role of ATM ATR gene on resistance of cancer stem cell subpopulations in advanced ovarian cancer: therapy response to in vitro apoptosis and proliferation

Introduction Approximately 85% of ovarian cancer patients were diagnosed at an advanced stage which has a high mortality rate. More than 80% of them respond to first-line chemotherapy using platinum-based regimen. However, the median disease-free survival is only 18 months. Most patients relapse and do not respond to subsequent lines of chemotherapy. Intervening the presence of cancer stem cells (CSC) is preferred in managing chemoresistant ovarian cancer. One of chemoresistance mechanisms identified in CSC is the high activity of ATM and ATR proteins that bind competitively to DNA against platinum-based regimen. Therefore, this study aimed to explore correlation of ATM and ATR gene expression in ovarian cancer CSC chemoresistance. Methods The culture cells of 67 advanced ovarian cancer patients were sorted using MACS with the CD133 marker to obtain CSC. The obtained CSCs were prepared with the spheroid method (using SKOV3 cell line, OV1, and OVM1). They were then tested with RT-qPCR (ATM, ATR, NANOG, ADAM19, Ki-67, and Caspase-3) and chemoresistance test (to carboplatin chemotherapy). Results It was found that the number of spheroids obtained, all gene expression, and number of chemoresistance to carboplatin regimen in CD133+ CSC cultures were higher than the main population and CD133-. CSCs with CD133+ had a higher ability to proliferate with increased Ki-67 gene expression, stronger stemness with higher NANOG gene expression, and greater chemoresistance ability with increased ATM and ATR gene. Conclusion/Implications It can be concluded that ATM and ATR gene expression are positively correlated with the resistance of CSC in ovarian cancer patients.