Junping Pan1, Chenglin Lu2, Wang Jun2, Yafu Wu2, Xiaolei Shi2, Yitao Ding1. 1. Department of Hepatobiliary Surgery, The Drum Tower Clinical Medical College, Nanjing Medical University Nanjing, Jiangsu Province, China. 2. Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing, Jiangsu Province, China.
Abstract
BACKGROUND: Sorafenib is one of the most commonly used systemic therapies for hepatocellular carcinoma (HCC), but the acquired resistance towards sorafenib found in HCC patients usually led to failure of treatment and poor prognosis. Therefore, there is an urgent need to study the molecular mechanism caused by the acquired resistance. Previous studies demonstrated that P62 plays an important role in tumor cell resistance towards systemic therapies including chemotherapy and targeted therapy. However, the role of P62 in acquired resistance to sorafenib in HCC has not been clearly investigated. MATERIALS AND METHODS: In this study we screened the most sensitive HCC cell lines towards sorafenib using CCK8. Then on this cell line, we analyzed the relationship between P62 expression level and the sensitivity towards sorafenib by western blot and CCK8. After knockdown and overexpression of P62 in HCC cells, cells were then treated with sorafenib. After that, we detect changes of sensitivity towards sorafenib. HCC samples were used to investigate the expression of P62 and their survival time. RESULTS: Among four HCC cell lines in our lab, HepG2 cell line with the highest sensitivity to sorafenib was screened and selected. After treatment with sorafenib, the expression of P62 was significantly increased. In HCC cells, we found that significant up-regulation of P62 was correlated with the reduction of sorafenib sensitivity. In HCC samples, we found that the expression of P62 was associated with sorafenib resistance and a shorter survival time. CONCLUSION: The up-regulation of P62 could reduce the sensitivity of HCC towards sorafenib. Thus, P62 could be therapeutic target to overcome sorafenib acquired resistance in the future. IJCEP
BACKGROUND:Sorafenib is one of the most commonly used systemic therapies for hepatocellular carcinoma (HCC), but the acquired resistance towards sorafenib found in HCCpatients usually led to failure of treatment and poor prognosis. Therefore, there is an urgent need to study the molecular mechanism caused by the acquired resistance. Previous studies demonstrated that P62 plays an important role in tumor cell resistance towards systemic therapies including chemotherapy and targeted therapy. However, the role of P62 in acquired resistance to sorafenib in HCC has not been clearly investigated. MATERIALS AND METHODS: In this study we screened the most sensitive HCC cell lines towards sorafenib using CCK8. Then on this cell line, we analyzed the relationship between P62 expression level and the sensitivity towards sorafenib by western blot and CCK8. After knockdown and overexpression of P62 in HCC cells, cells were then treated with sorafenib. After that, we detect changes of sensitivity towards sorafenib. HCC samples were used to investigate the expression of P62 and their survival time. RESULTS: Among four HCC cell lines in our lab, HepG2 cell line with the highest sensitivity to sorafenib was screened and selected. After treatment with sorafenib, the expression of P62 was significantly increased. In HCC cells, we found that significant up-regulation of P62 was correlated with the reduction of sorafenib sensitivity. In HCC samples, we found that the expression of P62 was associated with sorafenib resistance and a shorter survival time. CONCLUSION: The up-regulation of P62 could reduce the sensitivity of HCC towards sorafenib. Thus, P62 could be therapeutic target to overcome sorafenib acquired resistance in the future. IJCEP
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