PMID: 9177491Jan 1, 1997Paper

In vitro and in vivo modulation by rhizoxin of non-P-glycoprotein-mediated vindesine resistance

Journal of Cancer Research and Clinical Oncology
H AriokaN Saijo

Abstract

Rhizoxin is an antineoplastic drug that inhibits tubulin polymerization. In this study, we demonstrated that rhizoxin was approximately twice as active in vitro against a human small-cell lung cancer cell line with non-P-glycoprotein-mediated resistance to vindesine, H69/VDS, as against its parental line, H69. Tubulin polymerization in H69/VDS, demonstrated by Western blot analysis, was inhibited markedly by rhizoxin compared with that in H69, in a concentration-dependent manner. A drug-accumulation study showed that the intracellular rhizoxin level in H69/VDS was 15% lower than that in H69, whereas efflux from H69/VDS was enhanced slightly. These results indicate that enhanced inhibition of tubulin polymerization rather than increased intracellular drug concentration accounted for the higher sensitivity of H69/VDS to rhizoxin. In an experiment using mice with severe combined immunodeficiency and inoculated subcutaneously with H69/VDS, in vivo tumor growth was reduced markedly by three intermittent intraperitoneal doses of rhizoxin compared with that in mice inoculated with H69. Three weeks after the last rhizoxin dose, the relative treated/untreated tumor volumes were 0.29 for H69, but only 0.06 for H69/VDS, indicating that H6...Continue Reading

References

Nov 1, 1992·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H R HendriksG Schwartsmann
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Citations

Jan 14, 2010·The International Journal of Neuropsychopharmacology·Tomoyuki SaijoYoshiro Okubo

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