低频脉冲电场逆转MCF-7/ADR对高三尖杉酯碱和长春新碱的耐药性

为了探讨低频脉冲电场对人乳腺癌多药耐药细胞系MCF-7/ADR耐药性的逆转作用及机制,采用MTT比色法检测MCF-7/ADR的耐药指数和耐药性的逆转倍数,荧光显微镜观察脉冲电场对MCF-7/ADR细胞内DiOC2(3)(P-gp的特异性荧光底物)积累和外排的影响。结果发现,在低频脉冲电场不影响MCF-7/ADR细胞生长的情况下,不同时间的电场作用均能逆转MCF-7/A的多药耐药,对高三尖杉酯碱(HHT)耐药性的逆转倍数在1.429～1.848之间,对长春新碱(VCR)耐药性的逆转倍数在1.473～2.090之间,45min电场作用的逆转效果最好,其次是30min电场作用。药物积累和外排实验结果表明,脉冲电场作用45min能使细胞内的DiOC2(3)积累明显增加,而30min电场作用能显著抑制DiOC2(3)的外排。促进药物积累和抑制其外排可能是脉冲电场逆转多药耐药的机制之一。

Reversal Effects of Low-frequency Pulsed Electrical Field on Multidrug Resistance of MCF-7/ADR to HHT and VCR

In order to explore the reversal effect and mechanism of low-frequency pulsed electrical field (LF-PEF) on multidrug resistance (MDR) of MCF-7/ADR, MTT analysis was used to detect resistance factor (RF) and reversal index (RI). The accumulation and efflux of DiOC2(3) were studied by fluorescence microscopy. The results showed that LF-PEF could reverse the MDR under the condition which not influence the growth of MCF-7/ ADR. RI of HHT was between 1.429-1.848 while RI of VCR was between 1.473-2.090. The sensitivity of MCF-7/ADR to HHT and VCR were enhanced by 45 min exposure to LF-PEF best and the next was 30 min exposure. 45 min exposure to LF-PEF increased the accumulation of intracellular DiOC2(3) while 30 min exposure inhibited P-gp-dependent efflux of DiOC2(3). So promoting drug accumulation and inhibiting drug efflux may be one of reversal mechanism of LF-PEF on MDR.