Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma

Background Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients. Aim This study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer. Results The outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components. Conclusion These findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients.