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肺癌細胞株におけるMRP発現と薬剤感受性に関する検討：堀田尚勝、近森研一、松下昭夫、田端雅弘、小原弘之、木浦勝行、上岡博、原田実根（岡山大・医・二内）

Expression of multidrug resistance-associated protein (MRP) and its homologues did not predict drug sensitivity for human lung cancer cell lines. :Naokatsu HORITA, Kenichi CHIKAMORI, Akio MATSUSHITA, Masahiro TABATA, Hiroyuki KOHARA, Katsuyuki KIURA, Hiroshi UEOKA, Mine HARADA(Dept. of Med. II, Okayama Univ.)

To investigate a role of multidrug resistance protein (MRP) and its homologues in drug resistance, we examined MRP expression, p53 mutation, and sensitivity to anti-cancer agents in 22 human lung cancer cell lines; 12 small cell lung cancer (SCLC) and 10 non-small cell lung cancer (NSCLC). MRP protein expression was determined by Western blotting using MRPr1 monoclonal antibody and IC50 values of 20 anti-cancer agents were determined by MTT assay. MRP protein expression levels in NSCLC cell lines were significantly higher than those in SCLC cell lines (p<0.01). In NSCLC cell lines, IC50 values of SN-38 (active metabolite of irinotecan), vinblastine, and vincristine had marginal correlations with MRP protein expression levels. 4-HC also had a marginal correlation with expression levels of MRP and its homologues. In SCLC cell lines, though IC50 value of rhizoxin showed reciprocal correlation with MRP expression level, it was not considered meaningful because MRP protein expression was weak in SCLC cell lines. p53 mutation of the cell lines, determined by PCR-SSCP and subsequent direct sequencing, had no correlation with IC50s of the drugs or MRP protein expression. These results indicate that expression of MRP and its homologues do not predict drug sensitivity for human lung cancer cell lines.