卵巣明細胞腺癌培養細胞株に対する塩酸イリノテカン(CPT-11)および他剤との併用による抗腫瘍効果についての検討

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In this study, the antitumor efficacy of CPT-11 (7-ethyl-10- [4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) was evaluated, using two kinds of ovarian clear cell carcinoma cell line, RMG-II and OVAS-21. The growth-inhibition test by sulforhodamine B (SRB) assay was performed using CPT-11, SN-38 (active substance of CPT-11 in vivo), CDDP, ADM, MMC and VP-16. The growth-inhibitory effect of SN-38 combined with CDDP, ADM or MMC was evaluated by isobologram. Then the effect of SN-38/CDDP on cell cycle was analyzed by flow cytometry. In addition, the cytokilling activity was analyzed by colony-forming assay. Since SN-38 revealed the lowest GI50 value among the anti-cancer agents tested in this study, SN-38 was presumed to possess the strongest growth-inhibitory effect. Isobologram analysis indicated additive interaction of SN-38 in combination with CDDP and either of the other drugs for two cell lines. SN-38 mainly contributed to the inhibitory effect of DNA synthesis and cell cycle progression. On the other hand, CDDP contributed to the cytokilling effect. These two drugs may act on different points in cell kinetics, therefore may have showed the additive effect in isobologram analysis. The present study suggests that combination therapy with CPT-11 and CDDP is potentially useful in the treatment of ovarian clear cell carcinoma.
東京女子医科大学の論文
1997-12-25