CAJ | 학술논문

为寻找能有效逆转肿瘤细胞多药耐药性的药物,通过体外细胞实验对Ams-11、Fw-13、Tul-17三种中药制剂逆转肿瘤细胞多药耐药性的作用进行了分析.并用流式细胞仪测定了Tul-17处理细胞后药物累积程度的变化及细胞P糖蛋白表达情况.为进一步研究体外细胞实验筛选出的多药耐药逆转剂在体内的药效学,将其中Fw13用于人白血病K562/ADR裸鼠移植瘤逆转试验.结果:在无细胞毒性的剂量范围内,该三种中药制剂均能明显增强多药耐药细胞对抗癌药物的敏感性,而且其逆转作用呈剂量依赖关系.Tu-17处理后,K562耐药细胞表达的P糖蛋白较对照降低1.5倍,对罗丹明123的累积量是对照的2.5倍.用Fw13治疗人白血病K562/ADR裸鼠移植瘤,可将硫酸长春新碱(VCR)对K562/ADR的抑瘤率从19.79%提高到86.59%,与单独VCR治疗疗效有显著性差异(P＜0.05).结果表明,这三种中药制剂可望成为肿瘤多药耐药逆转剂,在肿瘤化疗中发挥作用.
위심조능유효역전종류세포다약내약성적약물,통과체외세포실험대Ams-11、Fw-13、Tul-17삼충중약제제역전종류세포다약내약성적작용진행료분석.병용류식세포의측정료Tul-17처리세포후약물루적정도적변화급세포P당단백표체정황.위진일보연구체외세포실험사선출적다약내약역전제재체내적약효학,장기중Fw13용우인백혈병K562/ADR라서이식류역전시험.결과:재무세포독성적제량범위내,해삼충중약제제균능명현증강다약내약세포대항암약물적민감성,이차기역전작용정제량의뢰관계.Tu-17처리후,K562내약세포표체적P당단백교대조강저1.5배,대라단명123적루적량시대조적2.5배.용Fw13치료인백혈병K562/ADR라서이식류,가장류산장춘신감(VCR)대K562/ADR적억류솔종19.79%제고도86.59%,여단독VCR치료료효유현저성차이(P＜0.05).결과표명,저삼충중약제제가망성위종류다약내약역전제,재종류화료중발휘작용.
The aim of this project was to find some kinds of Chinese medicines as effective agents for reversal of cancer multidrug resistance. Based on the present authors'previous researches,thirty-two kinds of Chinese medicines as research materials were selected and examined. Using cell growth inhibition assay,the authors found that three of them,Ams-11 ,Fw-13 and Tul17,in the doses free from cytotoxicity could enhance the senstivity of multidrug resistant cells to anticancer drugs in a dose-dependent way. Through mechanistic studies, the authors demonstrated that Tul-17 could increase the accumulation of MDR drugs,and attenuate the expression level of P-glycoprotein (Pgp).Animal test with Fw-13 also proved the MDR reversal effect of this medicine. Taken together,the resultsindicate that these three Chinese medicines might be potential effective MDR reversal agents.