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Asian Pacific Journal of Cancer Prevention
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Zhao, Y., Lau, L., Dai, X., Li, B. (2016). In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma. Asian Pacific Journal of Cancer Prevention, 17(11), 4853-4856. doi: 10.22034/APJCP.2016.17.11.4853
Youna Zhao; Lit-Fui Lau; Xiangrong Dai; Benjamin Li. "In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma". Asian Pacific Journal of Cancer Prevention, 17, 11, 2016, 4853-4856. doi: 10.22034/APJCP.2016.17.11.4853
Zhao, Y., Lau, L., Dai, X., Li, B. (2016). 'In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma', Asian Pacific Journal of Cancer Prevention, 17(11), pp. 4853-4856. doi: 10.22034/APJCP.2016.17.11.4853
Zhao, Y., Lau, L., Dai, X., Li, B. In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma. Asian Pacific Journal of Cancer Prevention, 2016; 17(11): 4853-4856. doi: 10.22034/APJCP.2016.17.11.4853

In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma

Article 9, Volume 17, Issue 11, November 2016, Page 4853-4856  XML PDF (474 K)
Document Type: Research Articles
DOI: 10.22034/APJCP.2016.17.11.4853
Authors
Youna Zhao 1; Lit-Fui Lau2; Xiangrong Dai3; Benjamin Li4
1Lees Pharmaceuticals
2CVie Therapeutics Limited, Taiwan,
3Zhaoke Pharmaceutical (Heifei) Co. Limited, Hefei, China
4Lee's Pharmaceutical (Hong Kong) Limited
Receive Date: 22 August 2016,  Revise Date: 14 November 2016,  Accept Date: 28 December 2016 
Abstract
 
Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.
Keywords
DNA topoisomerase I; Hepatocellular carcinoma; Antitumor; In vitro; in vivo
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