Knockdown of lncRNA TP53TG1 Enhances the Efficacy of Sorafenib in Human Hepatocellular Carcinoma Cells
Qingchun Lu, Mingyang Xin, Qian Guo, Brad S. Rothberg, Ana M. Gamero, Ling Yang
Abstract
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Qingchun Lu, Mingyang Xin, Qian Guo, Brad S. Rothberg, Ana M. Gamero, Ling Yang
Abstract
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The multikinase inhibitor, sorafenib, is a first-line treatment for hepatocellular carcinoma (HCC), but its limited efficacy, drug resistance and toxicity are a concern. In this study, we investigated the role of lncRNA TP53TG1 in the efficacy of sorafenib in HCC cells. We found that treatment with sorafenib increased the expression of TP53TG1 in HCC cells. Knockdown of TP53TG1 sensitized tumor cells to the antiproliferative effects of sorafenib. Furthermore, TP53TG1 knockdown had an additive inhibitory effect on HCC cell proliferation and migration in the presence of sorafenib. The combination of TP53TG1 knockdown and sorafenib drastically inhibited the activation of the ERK pathway. This work demonstrates that TP53TG1 deficiency enhances the efficacy of sorafenib in HCC. Combining TP53TG1 knockdown with sorafenib may be an optimal form of therapy for HCC treatment.
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The multikinase inhibitor, sorafenib, is a first-line treatment for hepatocellular carcinoma (HCC), but its limited efficacy, drug resistance and toxicity are a concern. In this study, we investigated the role of lncRNA TP53TG1 in the efficacy of sorafenib in HCC cells. We found that treatment with sorafenib increased the expression of TP53TG1 in HCC cells. Knockdown of TP53TG1 sensitized tumor cells to the antiproliferative effects of sorafenib. Furthermore, TP53TG1 knockdown had an additive inhibitory effect on HCC cell proliferation and migration in the presence of sorafenib. The combination of TP53TG1 knockdown and sorafenib drastically inhibited the activation of the ERK pathway. This work demonstrates that TP53TG1 deficiency enhances the efficacy of sorafenib in HCC. Combining TP53TG1 knockdown with sorafenib may be an optimal form of therapy for HCC treatment.
Key concepts: Sorafenib, Gene knockdown, Hepatocellular carcinoma, Cancer research, MAPK/ERK pathway, Medicine, Cell culture, Pharmacology