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目的耐药性是化疗失败的主要原因之一,克服耐药性的方法之一是使用逆转剂。目前尚无一理想的、可应用于临床的阿霉素(ADM)耐药逆转剂。本研究探讨聚束微波加热对ADM耐药性的逆转作用及其机制。方法体外利用人乳腺癌细胞株MCF-7的ADM耐药模型MCF-7/ADM,采用MTT法检测聚束微波加热对MCF-7/ADM细胞耐药性的逆转作用。用Real-Time PCR测定细胞P-糖蛋白(P-glycoprotein,P-gp)、多药耐药相关蛋白(Multidrug resistance relatedprotein,MRP)的表达水平。高效液相色谱法(HPLC)测定细胞内ADM浓度。结果MCF-7/ADM细胞对ADM的耐药指数为45.5。经聚束微波加热后,ADM对MCF-7/ADM的半数抑制浓度(IC_(50))由(60.56±2.38)ug/ml下降至(22.86±2.76)ug/ml,逆转倍数为2.64倍。Real-Time PCR检测结果显示,MCF-7/ADM细胞的MRP与P-gp mRNA表达水平均明显高于MCF-7细胞,经聚束微波加热后,MCF-7/ADM细胞胞内的MRP与P-gp mRNA表达水平均明显下降。HPLC法测定细胞内ADM含量的结果显示,经聚束微波加热处理后,MCF-7/ADM细胞内ADM的含量明显增加。结论聚束微波加热能逆转MCF-7/ADM对ADM的耐药性,聚束微波加热逆转ADM耐药性的机制可能是减少MCF-7/ADM细胞内MRP与P-gp mRNA的表达水平,从而增加了MCF-7/ADM细胞内ADM的蓄积。
The purpose of drug resistance is one of the major causes of chemotherapy failure, one of the ways to overcome resistance is the use of reversal agents. There is no ideal reversal agent for adriamycin (ADM) that can be applied to clinic. This study explored the reversal effect and mechanism of microwave irradiation on ADM resistance. Methods The drug-resistant MCF-7 / ADM cell line MCF-7 / ADM was used in vitro. MTT assay was used to detect the reversal of multidrug resistance in MCF-7 / ADM cells. Real-time PCR was used to detect the expression of P-glycoprotein (P-gp) and multidrug resistance related protein (MRP). Intracellular ADM concentration was determined by high performance liquid chromatography (HPLC). Results The drug resistance index of MCF-7 / ADM cells to ADM was 45.5. After concentrated microwave heating, the half inhibitory concentration (IC50) of ADM on MCF-7 / ADM decreased from (60.56 ± 2.38) ug / ml to (22.86 ± 2.76) ug / ml and the reversal fold was 2.64 times. Real-Time PCR results showed that MRP and P-gp mRNA expression levels in MCF-7 / ADM cells were significantly higher than those in MCF-7 cells. After microwave irradiation, the intracellular MRP and P-gp mRNA expression levels were significantly decreased. The results of HPLC assay of intracellular ADM showed that the content of ADM in MCF-7 / ADM cells increased significantly after microwave irradiation. CONCLUSIONS: Microwave irradiation can reverse the drug resistance of MCF-7 / ADM to ADM. The mechanism by which microwave irradiation can reverse ADM resistance may be to decrease the expression of MRP and P-gp mRNA in MCF-7 / ADM cells. Thereby increasing the accumulation of ADM in MCF-7 / ADM cells.