| ABSTRACTThe reverse study of the extractive of BanLanGen to human multidrug-resistant hepatocarcinoma cell BEL-7404/ADMObjective To study the reverse roles and mechanisms of the extractive of BanLanGen to human multidrug-resistant hepatocarcinoma cell BEL-7404/ADMMethods Human multidrug-resistant hepatocarcinoma cell line model BEL-7404/ADM was established through progressive increase of ADM concentration, which sensitivity to multianticancer agents was evaluated by MTT assay. The expressions of p-gp and MRP were detected by immunohistochemical method. The active monomers of BanLanGen were selected and their reverse roles to multidrug-resistance detected with MTT method. The content of ADM in cells was determined with high performance liquid chromatography (HPLCA). Results The human multidrug-resistant hepatocarcinoma cell line BEL-7404/ADM showed the drug resistance to adriamycin, mitomycin, hydroxycamptothecin, and the resistance index 100.03, 41.42, 90.65, respectively. The expressions of p-gp and MRP in BEL-7404/ADM were 68.79%, 53.50%, respectively, and significantly higher than in BEL-7404(P<0.01).Two active monomers of BanLanGen 5b and 5c selected with this model had cytotoxic role to BEL-7404 and BEL-7404/ADM in high concentration (>500μg/ml), whereas reverse role to ADM for BEL-7404/ADM in noncytotoxic concentration (<250μg/ml), which reverse times were 2~6. The ADM accumulation in BEL-7404 cells increased significantly(p<0.001) when ADM coupled with 5b or verapamil than used only, 56.875±9.349 pg,63.500±9.000pg, 19.625±0.629 pg, respectively.Conclusions BEL-7404/ADM established through progressive increase of ADM concentration is a multidrug resistant model, which multidrug-resistance is related with over-expressions of p-gp and MRP. Two active monomers of BanLanGen 5b and 5c can reverse resistance of BEL-7404/ADM, and the reverse role may be related with intracellular anticancer agents content increase.
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