PMID: 9525824Apr 3, 1998Paper

In vivo etoposide-resistant C6 glioma cell line: significance of altered DNA topoisomerase II activity in multi-drug resistance

Journal of Neuro-oncology
T TakiT Hayakawa

Abstract

We have established an in vivo etoposide-resistant glioma cell line (C6/VP) from C6 rat glioma cells by stepwise exposure to increasing doses of etoposide. The C6/VP cells were 10 times more resistant to etoposide than the parental C6 cells. In addition C6/VP cells demonstrated cross-resistance to vincristine and vinblastine, but not to ADM or m-AMSA. Interestingly, the cells had collateral sensitivity to ACNU, cisDDP and Ara-C. The C6/VP cells did not express the MDR gene or p-glycoprotein, while they showed 16 times less topoisomerase II catalytic activity compared to the C6 cells. Although there was no significant difference between C6 and C6/VP cells in amounts of topoisomerase II in nuclear extracts, the C6/VP cells had 2.9 times higher amounts of the enzyme than C6 cells in nuclear scaffold prepared from a relatively low-salt buffer (0.5 M NaCl). Northern blot analysis demonstrated that mRNAs of topoisomerase IIalpha isoforms were expressed both in C6 and C6/VP cells, and that the amounts of topoisomerase IIalpha in C6/VP cells were 14 times greater than in C6 cells. The total uptake of etoposide in tumor tissues derived from C6/VP cells was 3 times less than those derived from parental C6 cells. These results indicate th...Continue Reading

Citations

Oct 16, 2012·Journal of Biomedical Materials Research. Part a·Maïté CallewaertV Gaëlle Roullin
May 5, 2001·Brain Research. Brain Research Reviews·M Bredel
Sep 19, 2009·Trends in Pharmacological Sciences·Matthew D HallMichael M Gottesman

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