汉防己甲素的pH依赖性生理性耐药研究

目的 探讨生物碱类药物汉防己甲素在不同pH值条件下对肿瘤细胞增殖的抑制作用。方法 以人肝癌细胞HepG-2和大肠癌细胞SW116为研究对象，采用MTT法检测不同浓度汉防己甲素（2、4、8、16、32μg／ml）分别在pH值为7.4和6.8条件下对肿瘤细胞增殖的抑制作用。结果 随汉防己甲素药物浓度的升高，其抑制肿瘤细胞增殖的作用逐渐增强，当pH为7.4时，32μg／ml汉防己甲素对HepG-2细胞和SW116细胞抑制率分别为88.6％和96.3％；同时不同浓度汉防己甲素在肿瘤细胞外pH值由7.4降至6.8后，其对HepG-2细胞和SW116细胞的增殖抑制作用均有明显下降（P＜0.05）。结论 抗肿瘤生物碱类中药的疗效可能受到肿瘤局部低pH值的影响，pH依赖性生理性耐药可能参与了肿瘤细胞耐药过程。

The pH-induced physiological herb drug resistance of tetrandrine

Objective To investigate the inhibition effect of tetrandrine on tumor cells and checkout the pH-induced physiological herb drug resistance. Methods The MrIT assay was used to examine the antiproliferative activity of different concentration of tetrandrine solution （2, 4, 8, 16,32μg/ml） on HepG-2 and SWl16 cell lines in different extracellular pH respectively （7.4 and 6. 8 ）. Results The inhibition ratio depended on the concentration of the drug, the inhibition ratio of 32fxg/m1 tetrandrine solution was 88.6% and 96. 3% for HepG-2 and SW116 cell lines at 7.4 extracellular pH values. When the extracellular pH values was decreased from 7. 4 to 6. 8, the antiproliferative activity of tetrandrine was descent simultaneously （ P 〈 0. 05 ）. Conclusion The possibility of descending the therapeutic efficacy of weak-base drugs is relate to the extracellular pH. The acidutside plasmalemmal pH gradient of solid tumors maybe result in the resistances of weak-base anticancer herb drugs deserves investigation.