葡萄籽多酚对人乳腺癌细胞MCF-7/ADR在裸鼠体内的多药耐药逆转作用

目的　研究葡萄籽多酚 (GSP)对人乳腺癌耐阿霉素细胞MCF 7/ADR的体内多药耐药逆转作用。方法　采用人乳腺癌裸鼠移植瘤模型研究GSP对肿瘤多药耐药的体内逆转作用 ;采用流式细胞术测定不同用药P 糖蛋白 (Pgp)表达变化及肿瘤细胞凋亡率变化。 结果　体内裸鼠抑瘤实验显示GSP有一定抑瘤作用 ,抑制率为 18 35 % ,联合应用阿霉素 (ADR)可显著抑制肿瘤生长 ,2 0mg/kgGSP可有效逆转MCF 7/ADR细胞的耐药性 ,抑瘤率为 5 4 6 4 %。流式细胞术结果显示应用GSP后肿瘤细胞Pgp表达显著降低 ( 32 0 3± 2 0 9) ,与对照组 ( 5 5 13± 2 12 )相比差异有显著意义 (P <0 0 5 )。平均凋亡率为 15 12 %± 1 0 4 % ,显著高于对照组 9 0 7%± 0 4 3% (P <0 0 5 )。结论　GSP能在体内逆转MCF 7/ADR细胞的耐药性 ,其机制可能是通过抑制Pgp表达 ,并可能通过诱导肿瘤细胞凋亡来起作用

Reversal of multidrug resistance of MCF-7/ADR in nude mice by grape seed polyphenol

OBJECTIVE: To study the reversing effect of Grape seed polyphenol (GSP) on multidrug resistance of MCF-7/ADR cell in vivo. METHODS: The transplantable breast carcinoma cell line MCF-7/ADR model was established in BALB/C-nu/nu mice by subcutaneous implantation. Flow cytometry (FCM) was used to investigate the changes of Pgp expression and apoptosis rate after different drug treatment. RESULTS: GSP has some effect on inhibition of tumor growth (the rate of inhibition was 18.35%), and combined with adriamycin can significantly inhibit tumor growth in nude mice, 20 mg/kg GSP can effectively reverse the resistance of MCF-7/ADR cells to ADR in vivo, and the rate of inhibition was 54.64%. FCM results showed that the expression of Pgp was significantly decreased (32.03 +/- 2.09) After administration of GSP and ADR, there was distinct difference between it and control (55.13 +/- 2.12). The mean rate of apoptosis was 15.12% +/- 1.04%, and was significantly increased compared with control (9.07% +/- 0.43%), P < 0.05. CONCLUSION: GSP can effectively reversed the resistance of MCF-7/ADR cells in nude mice, the mechanism may be correlated with inhibition of Pgp expression and apoptosis.