目的通过选用甘草的主要单药活性成分作用于人宫颈癌HeLa细胞,探索其对硫氧还蛋白(thioredoxin-1,Trx)在肿瘤细胞核中定位的影响。方法选取甘草酸(glycyrrhizic acid,GCA)、甘草苷(liquiritin,LQ)两种单药分别设置药物浓度梯度与作用时间梯度实验组。再将一定浓度的GCA、LQ分别与临床化疗药物紫杉醇(paclitaxel,PTX)或表柔比星(epirubicin,EPI)两两联用设置联合用药实验组。通过Western blot测定Trx在HeLa细胞核中表达量的变化,四甲基偶氮唑盐(MTT)比色法检测药物对HeLa细胞增殖抑制的影响。结果 Trx在细胞核内的含量变化均随2种单药浓度的增大和药物作用时间的延长呈下降趋势;GCA、LQ对细胞的毒性较小,且其与低剂量化疗药物联用对细胞核中Trx表达量的影响,与单纯高剂量化疗药物作用效果相近。结论 GCA和LQ均可使Trx在HeLa细胞核中的表达下降,且其与临床化疗药物联用有望降低后者的使用剂量,从而表现出一定的潜在临床应用价值。
Objective To investigate the impact of active components of main single drugs from licorice on the expression of thioredoxin-l(Trx)in the nuclei of human cervical carcinoma HeLa cells. Methods The experimental groups were established according to the concentration gradient and different treatment time of glycyrrhizic acid(GCA)and liquiritin(LQ). Additionally, GCA and LQ at certain concentrations were separately combined with clinical chemotherapy drugs paclitaxel(PTX)or epirubicin (EPI)to set up the combined experimental groups. The changes of Trx expression levels in HeLa cell nuclei were measured by immunoblotting,and the effects of the drugs on cell proliferation were tested by methyl thiazolyl tetrazolium (MTT)as- say. Results The expression levels of Trx in the nuclei of HeLa cells were decreased in a dose- and time-dependent manner after treatment with GCA and LQ. Both GCA and LQ were found less toxic to cells. The effects of GCA and LQ combined with low- dose chemotherapy drugs on the expression levels of Trx were similar to those in high-dose chemotherapy drug groups. Conclusion GCA and LQ can decrease the Trx expression levels in HeLa cell nuclei. Their combination with clinical chemotherapy drugs are expected to reduce the dosage of chemotherapy drugs, which have great potential clinical application values.