Biochemical characterization of cisplatin-resistance in MKN-45 human stomach adenocarcinoma cell line.
We have established a cisplatin resistant subline, MKN/CDDP, from the MKN-45 human stomach adenocarcinoma cell line. MKN/CDDP was 10.7 fold more resistant to cisplatin, 5.4 fold resistant to carboplatin, 2.7 fold resistant to 5-fluorouracil and only 1.4 fold resistant to adriamycin. To investigate the mechanism of the cisplatin resistance in the MKN/CDDP subline, we performed the biochemical characterization of MKN-45 and MKN/CDDP. MKN/CDDP cells showed no induction in p-glycoprotein and topoisomerase II. The level of glutathione S-transferase-pi was higher in MKN/CDDP than the parent line, but a similar level of glutathione S-transferase-L isoform was observed. Superoxide dismutase activity was 1.67 fold higher in the MKN/CDDP subline than the parent line, but 60 kDa catalase was much lower in the MKN/CDDP subline. In addition to those changes. MKN/CDDP was not able to attach to the culture dish, which is probably due to the lack of fibronectin association on the cell surface. The MKN/CDDP subline revealed a variety of biochemical changes which are related to drug inactivation and to cell substratum adhesion. The significance of each modification in the development of the cisplatin resistance will be evaluated in future studies.
Department of Internal Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004790:Enzyme Induction; D005353:Fibronectins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D005353:Fibronectins; D004250:DNA Topoisomerases, Type II; D005978:Glutathione; D002945:Cisplatin