Reversal Effects Of Low-frequency Pulsed Electrical Field On Multidrug Resistance Of MCF-7/ADR To HHT And VCR

Multi-drug resistance (MDR) is an obstacle to succeed in chemotherapy of breast cancer. The anti-MDR drugs are the traditional method to reserve the MDR. But anti-MDR drugs also bring the adverse reaction when cure the breast cancer. Therefore there need a novel method to reverse the multi-drug resistance. It is explored the reversal effect and mechanism of low-frequency pulsed electrical field (LF-PEF) on multidrug resistance of MCF-7/ADR.To research the drug resistance reverse, MCF-7/ADR is established with higher drug resistance and higher P-gp expression as cell model. MTT analysis was used to detect the effect of LF-PEF on the MCF-7/ADR cell growth. We select the lowest inhibition of cells growth as the best electrical treatment way on the anti-MDR research. MTT analysis was also used to select best electrical work time to reversal MDR. The accumulation and efflux of DiOC2₃ which is the specific substrate of P-gp were studied by fluorescence microscopy.The high MDR MCF-7/ADR was established by touching cells with lower concentration ADR. The established MCF-7/ADR resistance ADR is 12.582 times higher than the pre-established cells, and which for DNR is 2.765 times. And the established MCF-7/ADR also has great higher resistance factor of HHT and VCR, which are 37.141 and 620.558. The DiOC2₃ accumulation decreased in established MCF-7/ADR in 210 minutes. So it is indicted that the P-gp had over expression.There are three LF-PEF methods in this study. The effect of LF-PEF on the MCF-7/ADR cell (Electric Group II) was the extremely same as the MCF-7/ADR growth regulation, P > 0.01 (besides of 45min). The effect of LF-PEF on the MCF-7/ADR cell and cell culture medium (Electric Group I) inhibits cell growth extremely, P < 0.05. And the effect of LF-PEF on the cell culture medium (Electric Group III) promote the breast cancer cell growth in long time treat (t = 15min, 30min and 45 min). Therefore, Electric Group II is the best LF-PEF treatment method to reverse the MDR, which is none growth effect on the MCF-7/ADR cell. Electric Group I is a good method to cure the cancer cell, which works on kill and inhibition the cell. And Electric Group III cannot be used to treat cancer cell, which effect on promoting the cell growth.The results showed that LF-PEF (Electric Group II) could reverse the MDR under the condition without 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 45min exposure to LF-PEF best and the next was 30min exposure. 45min exposure to LF-PEF increased the accumulation of intracellular DiOC2₃ while 30min exposure inhibited P-gp-dependent efflux of DiOC2₃. So promoting drug accumulation and inhibiting drug efflux may be one of reversal mechanism of LF-PEF on MDR. Conclusions are as below.(1) The drug resistance MCF-7/ADR can be established by treatment low concentration ADR.(2) The effect of LF-PEF on MCF-7/ADR cell (Electric Group II) is almost same as the normal MCF-7/ADR cell growth regular. Therefore this electric treat method can be used to reverse the MDR of MCF-7/ADR.(3) The effect of LF-PEF on MCF-7/ADR cell and cell culture medium (Electric Group I) is to inhibit the cell growth, so it can be used to cure the normal cancer cell.(4) The effect of LF-PEF on cell culture medium is to promotion the cell growth, so it can not be used to treat the cancer cells.(5) The MCF-7/ADR MDR can be reversed by Electric Group II. The sensitivity of MCF-7/ADR to HHT and VCR were enhanced by 45min exposure to LF-PEF best and the next was 30min exposure.(6) 45min exposure to LF-PEF increased the accumulation of intracellular DiOC2₃ while 30min exposure inhibited P-gp-dependent efflux of DiOC2₃. So promoting drug accumulation and inhibiting drug efflux may be one of reversal mechanism of LF-PEF on MDR.