Year-end Sale % OFF 
Abstract
Abstract Aims: Hepatocellular carcinoma (HCC) is the fifth cause of cancer death all over the world and its prognosis is very poor. To improve the prognosis of HCC patients, a novel therapy including chemotherapy against HCC should be developed. The strategies to enhance the efficacy of anticancer drugs are required. Sorafenib is the only drug to prolong overall survival of the patients with HCC, however, the outcome is not still satisfactory. In this study, we investigated the effects of combination treatment of anticancer drugs and retinoids,which has been known to show antitumor activity, in HCC cells. Methods: Cytotoxicity of combination treatment of retinoids (all-trans retinoic acid (ATRA), NIK-333 and Am80) and anticancer drugs (sorafenib, adriamycin, cisplatin, mitomycin C and 5-FU) was examined by cell viability assay. The effect on energy metabolic pathway, such as AMPK activation, intracellular ATP level, and the expression of glycolytic and TCA cycle genes were examined in HepG2 cells treated with sorafenib alone or in combination with retinoids. Induction of apoptosis was evaluated in the cells treated with the combination treatment of sorafenib and ATRA. Results: ATRA enhanced the cytotoxic effects of all 5 anticancer drugs tested, being much more effective than NIK-333 andAm80.AMPK activation, reduction of ATP content, and downregulation of glycolytic genes GLUT-1 and LDHA were observed in the cells treated with ATRA alone or in combination with sorafenib. In the combination treatment, increased apoptosis which was followed by activation of p38MAPK and JNK, upregulation and translocation of Bax to mitochondria, and activation of caspase-3 was observed. Conclusion: ATRA is useful for enhancing the cytotoxicity of antitumor drugs for HCC by regulating energy metabolism in HCC cells. Citation Format: Goshi Shiota, Hiroki Shimizu, Keita Kanki. Suppression of glycolysis by retinoic acid sensitizes hepatocellular carcinoma cells to apoptosis induced by sorafenib via AMPK activation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 708A. doi:10.1158/1538-7445.AM2015-708A
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
