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P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine).

Publication ,  Journal Article
Adams, DJ; Knick, VC
Published in: Invest New Drugs
1995

Navelbine (NVB, vinorelbine tartrate) is a semisynthetic Vinca alkaloid in which the catharanthine moiety contains an eight-membered ring in place of the nine-membered ring that is present in all naturally occurring members of the vinblastine group. This modification selectively reduces interaction with anoxal vs mititotic microtubules and may account for the lower neurotoxicity with improved antitumor activity that has been observed in clinical trials with breast, lung and ovarian cancer. We were interested in whether the structural modification in NVB would also alter the drug resistance profile. Specifically, our aim was to determine whether NVB, like vinblastine (VBL), participates in P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). NVB-resistant, murine P388 cells (P388/NVB), were derived in vivo and used in conjunction with a battery of drug-resistant P388 cell lines in vivo and murine and human tumor cell lines in vitro to develop a resistance profile for NVB. P388/NVB bells were cross-resistant to drugs involved in MDR (doxorubicin, etoposide, amsacrine, vinblastine, vincristine and actinomycin D), but not to the alkylating agents, cyclophosphamide, carmustine, and cisplatin, or to the antimetabolites, 5-fluorouracil and methotrexate. P388/NVB cellular resistance to NVB was stable without drug pressure during continuous passage in vivo for more than ten weeks and in vitro for at least five weeks. These cells exhibited increased expression of P-gp, and a 30-fold level of resistance of NVB in vitro, which was completely reversable with verapamil. The MDR phenotype was confirmed in other tumor models. P388 tumors resistant to vinblastine, vincristine, doxorubicin, and etoposide were cross-resistant to NVB in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Published In

Invest New Drugs

DOI

ISSN

0167-6997

Publication Date

1995

Volume

13

Issue

1

Start / End Page

13 / 21

Location

United States

Related Subject Headings

  • Vinorelbine
  • Vinblastine
  • Verapamil
  • Tumor Cells, Cultured
  • Oncology & Carcinogenesis
  • Mice
  • Male
  • Leukemia, Experimental
  • Humans
  • Drug Resistance, Neoplasm
 

Citation

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MLA
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Adams, D. J., & Knick, V. C. (1995). P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine). Invest New Drugs, 13(1), 13–21. https://doi.org/10.1007/BF02614215
Adams, D. J., and V. C. Knick. “P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine).Invest New Drugs 13, no. 1 (1995): 13–21. https://doi.org/10.1007/BF02614215.
Adams DJ, Knick VC. P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine). Invest New Drugs. 1995;13(1):13–21.
Adams, D. J., and V. C. Knick. “P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine).Invest New Drugs, vol. 13, no. 1, 1995, pp. 13–21. Pubmed, doi:10.1007/BF02614215.
Adams DJ, Knick VC. P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine). Invest New Drugs. 1995;13(1):13–21.
Journal cover image

Published In

Invest New Drugs

DOI

ISSN

0167-6997

Publication Date

1995

Volume

13

Issue

1

Start / End Page

13 / 21

Location

United States

Related Subject Headings

  • Vinorelbine
  • Vinblastine
  • Verapamil
  • Tumor Cells, Cultured
  • Oncology & Carcinogenesis
  • Mice
  • Male
  • Leukemia, Experimental
  • Humans
  • Drug Resistance, Neoplasm