Cisplatinum (CDDP) 討入 Liposome の培養神経芽腫細胞への抗腫瘍効果

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  • Growth Inhibition of Human Neuroblastoma IMR-32 by Liposome-Encapsulated Cisplatinum

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The therapeutic usefulness of cisplatinum (CDDP) as an anticancer agent has been well documented, but the serious nephrotoxicity remains as major hazard in clinical use. Liposome-encapsulated cisplatinum (CDDP-liposome) was employed to arrest the aberrant growth of cultured Human neuroblastoma cells IMR-32, and further to reduce the side effect of CDDP for its clinical use. CDDP-liposome was prepared by the modified Forssen's method (Cancer Rec. 43, 546-550, 1983), i.e. ,phosphatidylcholine (PC) : phosphatidylserine (PS): cholesterol =6: 2: 3 on molar ratio. After sonication CDDP-liposome was separated from free drug by gelfiltration (Sephadex G-50). CDDP-liposome dose-dependently inhibited the cell growth of IMR-32 in a similar fashion to free CDDP. While 2.0μg/ml of free CDDP induced 50% inhibition of DNA synthesis (ID50) of IMR-32, only 0.7μg/ml of CDDP encapsulated in liposome, approximately 1/3 concentration as high as free CDDP, did ID50. In contrast, CDDP-liposome showed a lower inhibitory effect on normal mouse fibroblast 3T3 (ID50: above 10.0μg/ml) than free CDDP, but on rat normal glioblast required almost same drug-dose as free CDDP. CDDP-liposome gave rise to 3-fold higher incorporation (1.4μg CDDP/mg protein) into IMR-32 than that of free CDDP (0.5μg CDDP/mg protein) at the same CDDP concentration (30.0μg/m/). These results suggest that CDDP-liposome, showing an effective growth inhibition through the selective drug-incorporation, is applicable to clinical use for neuroblastoma in the future.

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