关键词: 乳腺癌, 补骨脂素, 脂筏, P-gp, 小窝蛋白-1

Abstract: To explore the effect of psoralen on reversing P-gp-mediated breast cancer resistance by reducing caveolin-1.We assessed cell viability by MTT assay to evaluate the cytotoxicity and multidrug resistance reversal activity of psoralen.We analysed the cellular accumulation of ADR and Rh 123 by immunofluorescence.We measured P-gp ATPase activity by monitoring ATP consumption.The effect of psoralen on P-gp and caveolin-1 expression were detected by RT-PCR and Western Blot.The effect of psoralen on P-gp and caveolin-1 co-localization by immunofluorescence.The IC₅₀ of MCF-7/ADR were 75.32±2.52 μg/mL,and the IC₅₀ of MCF-7/ADR+psoralen were 24.28±1.53 μg/mL (P<0.05).The relative fluorescence intensity of ADR in MCF-7/ADR+psoralen is 60.03%±2.89% and higher than the MCF-7/ADR 24.59%±1.29% (P< 0.05).The relative fluorescence intensity of Rh123 in MCF-7/ADR+psoralen is 67.8%±3.03% and significantly higher than the control group 23.69%±1.28% (P<0.01).Psoralen significantly decreased ATPase activity of P-gp (P<0.05).Psoralen did not affect the protein expression or mRNA levels of P-gp (P> 0.05).The expression of caveolin-1 was down-regulated in MCF-7/ADR+psoralen cells (P<0.05).Compared with cells without psoralen,the relative fluorescence intensity was decreased by 0.56-fold in cells treated with 8 μg/mL psoralen (P<0.05).Psoralen reduces multidrug resistance by inhibiting the efflux function of P-gp,which may be important for increasing the efficiency of chemotherapy and improving the clinical protocols aiming to reverse P-gp-mediated multidrug resistance.

Key words: breast cancer, lipid rafts, P-gp, caveolin-1, psoralen