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

AbstractAIM:
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).
MATERIALS AND METHODS:
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.
RESULTS:
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.
CONCLUSION:
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
Topics
  • 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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