Knockdown of 14-3-3ζ enhances radiosensitivity and radio-induced apoptosis in CD133+ liver cancer stem cells

14-3-3ζ is related to many cancer survival cellular processes. In a previous study, we showed that silencing 14-3-3ζ decreases the resistance of hepatocellular carcinoma (HCC) to chemotherapy. In this study, we investigated whether silencing 14-3-3ζ affects the radioresistance of cancer stem-like cells (CSCs) in HCC. Knockdown of 14-3-3ζ decreased cell viability and the number of spheres by reducing radioresistance in CSCs after γ-irradiation (IR). Furthermore, the levels of pro-apoptotic proteins were upregulated in CSCs via silencing 14-3-3ζ after IR. These results suggest that 14-3-3ζ knockdown enhances radio-induced apoptosis by reducing radioresistance in liver CSCs. Targeting a key regulatory protein enhances the sensitivity of liver cancer stem cells (CSCs) to radiation, researchers in South Korea have shown. Seung Kew Yoon and his colleagues at the department of internal medicine of the Catholic University in Seoul exposed CSCs derived from a human liver tumor cell line to γ-irradiation. They observed an increase in the expression of 14-3-3ζ, a protein that controls many processes important in cancer biology, such as programmed cell death. Next, the team added virus vectors engineered to express RNA molecules that silence the gene that encodes the 14-3-3ζ protein. In response, the liver CSCs displayed a decrease in cell viability and an increase in the concentration of proteins involved in cell death. The authors conclude that suppressing 14-3-3ζ expression may augment the therapeutic efficacy of radiation therapy for liver cancer patients.