title: In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma
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.
authors.affiliation: Lee's Pharmaceutical (Hong Kong) Limited, Hong Kong,China. Email: youna.zhao@leespharm.com
authors.forename: Youna
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lit-Fui
authors.initials: LF
authors.lastname: Lau
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Dai
authors.forename: Benjamin
authors.initials: B
authors.lastname: Li
keywords: Gimatecan; DNA topoisomerase I; hepatocellular carcinoma; antitumor; in vitro; in vivo