^(99m)锝-甲氧基异丁基异腈在人肺癌细胞中的摄取与肺癌细胞耐药间的关系及二氯乙酸盐对肺癌细胞耐药的影响

The uptake of ^(99m)Tc methoxyisobutylisonitrile in human lung adenocarcinoma cells is associated with changes of cellular drug resistance induced by dichloroacetate

目的:探讨99m锝-甲氧基异丁基异腈(technetium-99m methoxyisobutylisonitrile,99mTc-MIBI)在人肺腺癌细胞株A549及其紫杉醇耐药株A549/taxol中的摄取与肺癌耐药之间的关系,以及二氯乙酸盐(dichloroacetate,DCA)对A549和A549/taxol细胞耐药的影响。方法:用CCK-8法检测不同浓度DCA对A549/taxol细胞生长的影响以及不同浓度紫杉醇单独或联合DCA(10mmol/L)对A549和A549/taxol细胞的半数抑制浓度(half inhibitory concentration,IC50)值。γ计数器检测DCA(10mmol/L)作用后A549和A549/taxol细胞对99mTc-MIBI的清除情况。结果:DCA≤10mmol/L时,对A549/taxol细胞无明显毒性作用。紫杉醇对A549/taxol细胞的IC50值明显高于对A549细胞(P<0.01);与紫杉醇单独作用组比较,A549/taxol细胞紫杉醇联合DCA组的IC50值下降(P<0.01)。A549/taxol细胞对99mTc-MIBI的清除率高于A549细胞(P<0.01),DCA处理后可使A549/taxol细胞对99mTc-MIBI的清除率下降(P<0.05);DCA并不影响A549细胞对99mTc-MIBI的清除率。结论:低毒浓度DCA可有效逆转A549/taxol细胞对紫杉醇的耐药,99mTc-MIBI的清除率可用于检测A549/taxol细胞的耐1药情况。

Objective：To investigate the correlation between the uptake of technetium99m methoxyisobutylisonitrile（99mTcMIBI） and drug resistance in A549 and A549 taxolresistant（A549/taxol） human lung adenocarcinoma cells,and to determine the effect of dichloroacetate（DCA） on cellular drug resistance.Methods：The growth rates of A549/taxol cells treated with DCA at different concentrations were determined by CCK8（cell count kit8） assay,and the growth rates of A549 and A549/taxol cells treated with taxol alone or at different concentrations combined with DCA（10 mmol/L） were also determined by CCK8 assay.The half inhibitory concentration（IC50） value of taxol was calculated.The clearance rates of 99mTcMIBI in A549 and A549/taxol cells were detected by γcounter after treatment with DCA（10 mmol/L）.Results：In A549/taxol cells,there was no evidence of cell toxicity induced by DCA（≤10 mmol/L）.The IC50 value of taxol was higher in A549/taxol cells than that in A549 cells（P0.01）.Compared with taxol treatment alone,the IC50 value of taxol in A549/taxol cells treated with taxol plus DCA（10 mmol/L） was significantly downregulated（P0.01）.The clearance rate of 99mTcMIBI was significantly higher in A549/taxol cells than that in A549 cells（P0.01）,and which could be downregulated after treatment with DCA（10 mmol/L） in A549/taxol cells（P0.05）.However,DCA had no effect on the clearance rate of 99mTcMIBI in A549 cells.Conclusion：DCA at a low concentration（10 mmol/L） can reverse the taxolresistance in A549/taxol cells,and this effect can be examined by clearance rate of 99mTcMIBI.