HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

In vivo circumvention of vincristine resistance in mice with P388 leukemia using a novel compound, AHC-52.

Abstract
A novel compound partially analogous to nifedipine, AHC-52, was found to sensitize multidrug-resistant tumor cells. AHC-52 at 0.5 microgram/ml completely reversed the in vitro resistance to vincristine (VCR) in VCR-resistant P388 cells (P388/VCR). Of various regimens examined for the in vivo treatment of P388/VCR-bearing mice, the combination of 0.05 mg/kg of VCR with 100 mg/kg twice a day of AHC-52 daily demonstrated the best result with a 206% increase in life prolongation. This result was comparable with that observed in parental P388-bearing mice treated with the optimal dose of VCR alone, indicating almost complete circumvention of resistance by combination VCR-AHC-52 therapy. In addition, the combination of both agents exhibited therapeutic effects in the treatment of P388-bearing mice with some long term survivors. This result was presumably due to the elimination of heterogeneity of VCR sensitivity in this cell population. These results suggest that combination chemotherapy using a sensitizing agent such as AHC-52 will be effective in not only circumvention of multidrug resistance but also retardation of its occurrence.
AuthorsH Shinoda, M Inaba, T Tsuruo
JournalCancer research (Cancer Res) Vol. 49 Issue 7 Pg. 1722-6 (Apr 01 1989) ISSN: 0008-5472 [Print] United States
PMID2924316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dihydropyridines
  • Pyrazoles
  • AHC 52
  • Vincristine
  • Nifedipine
Topics
  • Animals
  • Dihydropyridines (pharmacology)
  • Drug Resistance
  • Drug Synergism
  • Female
  • Leukemia P388 (drug therapy)
  • Leukemia, Experimental (drug therapy)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Nifedipine (analogs & derivatives)
  • Pyrazoles (pharmacology)
  • Vincristine (therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: