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Reversal mechanism of Tetradrine on human pancreatic carcinoma multi-drug resistance cell line SW1990-GEM

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  • Received:2012-01-17 Revised:2012-10-13 Published:2013-01-15 Online:2013-01-15

Abstract: Reversal mechanism of Tetradrine on human pancreatic carcinoma multi-drug resistance cell line SW1990-GEM Abstract Objective To investigate the reversal effects of Tetradrine (Tet)on human pancreatic carcinoma multidrug resistance cell line SW1990-GEM and the mechanism involved in this reversal. Methods Immunocytochemistry was used to test the expression of P-glycoprotein(P-gP) coded by the multidrug resistance-1 gene of SW1990-GEM cells. The inhibitory effects of Tet on the proliferation of SW1990-GEM cells were evaluated by MTT assay, IC50 and reversal fold were computed. The effects of noncytotoxicity of TET on Rhodamin123 accumulation in SW1990-GEM cells was analyzed by Flow Cytometry. The effects of Tet on the expression of P-gP was detected by Western Blot. Results The expression of P-gP in SW1990-GEM cells were higher than that of SW1990 cells. Noncytotoxicity of Tet possessed reversal effects on SW1990-GEM cells. Tet increased significantly intracellular chemotherapeutical drug accumulation in SW1990-GEM cells. The resistance index of SW1990-GEM cells to Gem was 217.91, when added 1.5 mg/L Tet, the resistance index was 24.32. The reversal folds was 8.96. Tet did not diversify the expression level of P-gp in SW1990-GEM cells. Conclusion Tet significantly reversed MDR of SW1990-GEM cells to enhance accumulation of chemotherapeutical drug in cells and increase its antitumor function.This mechanism seems Tet directly inhibited transport function of P-gp, but it did not alter the protein expression level of P-gp.

Key words: Pancreatic carcinoma, multi-drug resistance cell, Tetrandrine, Modulator