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

  • 발행 : 2016.11.01


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.


  1. Brown KS (2006). Chemotherapy and other systemic therapies for hepatocellular carcinoma and liver metastases. Semin Intervent Radiol, 23, 99-108.
  2. Cheng AL, Kang YK, Lin DY, et al (2013). Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial. J Clin Oncol, 31, 4067-75.
  3. Giglia JL, Antonia SJ, Berk LB, et al (2010). Systemic therapy for advanced hepatocellular carcinoma: past, present, and future. Cancer Control, 17, 120-9.
  4. He AR, Goldenberg AS (2013). Treating hepatocellular carcinoma progression following first-line sorafenib: therapeutic options and clinical observations. Therap Adv Gastroenterol, 6, 447-58.
  5. Johnson PJ, Qin S, Park JW, et al (2013). Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study. J Clin Oncol, 31, 3517-24.
  6. Mikhail S, Cosgrove D, Zeidan A (2014). Hepatocellular carcinoma: systemic therapies and future perspectives. Expert Rev Anticancer Ther, 10, 1205-18.
  7. Mor E, Tur-Kaspa R, Sheiner P, Schwartz M (1998). Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation. Ann Intern Med, 129, 643-53.
  8. Pecorelli S, Ray-Coquard I, Tredan O, et al (2010). Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes. Ann Oncol, 21, 759-65.
  9. Pratesi G, De Cesare M, Carenini N, et al (2002). Pattern of antitumor activity of a novel camptothecin, ST1481, in a large panel of human tumor xenografts. Clin Cancer Res, 8, 3904-9.
  10. Pratesi G, Beretta GL, Zunino F (2004). Gimatecan, a novel camptothecin with a promising preclinical profile. Anticancer Drugs, 15, 545-52.
  11. Qin SK (2012). Guidelines on the diagnosis and treatment of primary liver cancer. Chin Clin Oncol, 1, 1-32.
  12. Qin SK, Bai Y, Lim HY, et al (2013). Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol, 31, 3501-8.