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Vol. 40 No. 1, 2001
Characterization of Drug Resistance to VM-26 in A2780 Ovarian Carcinoma Cells
Chun-Mao Lin1,2, Tzong-Yueh Chen2, Leng-Fang Wang1, Cho-Fat Hui3,* and Jaulang Hwang2,*
1Department of Biochemistry, Taipei Medical College, Taipei, Taiwan 110
2Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 115
3Institute of Zoology, Academia Sinica, Taipei, Taiwan 115
Chun-Mao Lin, Tzong-Yueh Chen, Leng-Fang Wang, Cho-Fat Hui and Jaulang Hwang (2001)
Human ovarian carcinoma A2780 cells resistant to VM-26, a topoisomerase
II-targeting drug, were cloned. Cross-resis- tance test showed that the
resistant cells were 300 fold more tolerant toward VM-26 than were
parental cells, whereas tolerance towards other drugs increased only 3
to 10 fold. VM-26 triggered apoptosis in a variety of cells including
rodent cells, but not in resistant cells. This resistance might not be
due to multidrug resistance (MDR). The topoisomerase II mRNA levels
showed only a slight variation between VM-26-treated and -untreated
resis- tant cells, and the difference in protein levels was about 2
fold. This implies that the level of topoisomerase II expression may
be unrelated to drug resistance. The DNA strand-passing activity of
topoisomerase II affected by VM-26 was measured by K-SDS precipitation
of the topoisomerase II-DNA complex, and topoisomerase II decatenation
of kinetoplastic DNA (K-DNA). The results showed that the VM-26
influence on topoisomerase II cleavable activity was much less in
resistant cells. Alteration of drug targeting sites in topoisomerase II
might be a factor contributing to VM-26 drug resistance in these
resistant cells.
Key words: Topoisomerase II, Drug resistance, VM-26.
*Correspondence: Tel: 886-2-27899512, 886-2-27899217. Fax: 886-2-27858059, 886-2-27826085. E-mail: JH@ccvax.sinica.edu.tw
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