Enhanced efficacy of CKD-516 in combination with doxorubicin: pre-clinical evaluation using a hepatocellular carcinoma xenograft model.

To evaluate the anticancer efficacy of CKD-516, a novel vascular-disrupting agent, alone and in combination with doxorubicin in the treatment of hepatocellular carcinoma (HCC).
In mice bearing luciferized HCC cells, therapeutic efficacy was assessed for seven days after single administration of CKD-516, doxorubicin, or combination of CKD-516 and doxorubicin.
Bioluminescence-imaging (BLI) signals in the CKD-516 group abruptly decreased initially, but recovered at seven days after treatment. BLI signals in the doxorubicin group gradually decreased over the 7-day period. In the combination group, BLI signals were abruptly reduced and remained suppressed for the 7-day period. On histopathological examination, CKD-516-treated tumors showed extensive central necrosis, whereas the peripheral layers remained viable. Doxorubicin-treated tumors showed mild and scattered necrosis. Tumors from the combination group showed more extensive central and peripheral necrosis, with smaller viable peripheral layers than the CKD-516 group.
Combination therapy can have additive effects for treatment of HCC compared with CKD-516 or doxorubicin monotherapy.
AuthorsYoung Il Kim, Kyung Won Kim, Han Kyu Lee, Jisuk Park, Jin Wook Chung, Hyewon Youn, Soo Jin Kim, Dal-Hyun Kim, Jen-Chieh Tseng, Jeong Min Lee
JournalAnticancer research (Anticancer Res) Vol. 34 Issue 4 Pg. 1715-22 (Apr 2014) ISSN: 1791-7530 [Electronic] Greece
PMID24692701 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzophenones
  • N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide
  • Doxorubicin
  • Valine
  • Animals
  • Apoptosis (drug effects)
  • Benzophenones (administration & dosage, pharmacology)
  • Carcinoma, Hepatocellular (drug therapy, pathology)
  • Cell Line, Tumor
  • Disease Models, Animal
  • Doxorubicin (administration & dosage, pharmacology)
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Humans
  • Liver Neoplasms (drug therapy, pathology)
  • Mice
  • Necrosis
  • Neovascularization, Pathologic (drug therapy)
  • Tumor Burden (drug effects)
  • Valine (administration & dosage, analogs & derivatives, pharmacology)
  • Xenograft Model Antitumor Assays

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