Objective: To determine the resistance reversion of mitomycin (MMC) by 3'-Keto-bmt1-val2-cyclosporin (SDZ PSC 833) in human cervical cancer in vitro and in vivo. METHEDS: A xenografted mitomycin resistant mice model of cervical cancer was devolped. The reversion of mitomycin resistance by SDZ PSC 833 (1 or 3 mg/L) was detected from human cervical cancer cell (Hela) and its resistant subline Hela/MMC in vitro and in vivo. Studies in vitro include drug resistance reversion experiment and the changes of morphology. Studies in vivo including tumor volume and tumor related histopathological changes in the autopsied specimen were evaluated by comparing random sections of each group.
Results: Nontoxic doses of SDZ PSC 833 could result in almost partial reversion of MMC-resistance of Hela/MMC. In vivo studies also showed SDZ PSC 833 augmented the growth inhibitory effect of mitomycin on Hela/MMC xenografted in nude mice.
Conclusion: SDZ PSC 833 can overcome mitomycin resistance of Hela/MMC in vitro and in vivo, so SDZ PSC 833 will be a better candidate clinically for reversing multidrug resistance.