PIC-BE诱导K562/ADM细胞凋亡及逆转其MDR的研究  

Studies of PIC BE on Induction of Apoptosis and Reversal of Multidrug resistance in K562/ADM Cell Line

作　　者：卢步峰[1] 杨佩满[1] 于丽敏[1] 王淑婷 郝立宏[1] 朱正美[1] 

机构地区：[1]大连医科大学辽宁省细胞分子生物学重点实验室

出　　处：《中国生物化学与分子生物学报》1999年第2期323-327,共5页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金

摘　　要：β榄香烯吗素（ＰＩＣ－ＢＥ）是抗癌新药β榄香烯的水溶性衍生物．采用人红白血病的多药耐药性（ＭＤＲ）细胞株Ｋ５６２／ＡＤＭ作为实验模型，观察ＰＩＣ－ＢＥ对Ｋ５６２／ＡＤＭ细胞的生长抑制和凋亡诱导作用，并进而研究其对该细胞ＭＤＲ的可能影响．结果显示：（１）Ｋ５６２／ＡＤＭ细胞对ＡＤＭ具有明显的抗性，与Ｋ５６２细胞相比，抗性倍数约为４０倍，而两者对ＰＩＣ－ＢＥ的ＩＣ５０接近，无显著差异；（２）ＰＩＣ－ＢＥ（１０．０～３０．０μｇ／ｍｌ）对Ｋ５６２／ＡＤＭ细胞具有明显的生长抑制和凋亡诱导作用，两种作用的强度在一定的范围内均具药物浓度和作用时间依赖性；（３）低毒剂量ＰＩＣ－ＢＥ（１０．０μｇ／ｍｌ）与ＡＤＭ（４．０μｇ／ｍｌ）联合应用，可显著增强ＡＤＭ对该细胞的生长抑制和凋亡诱导作用，升高细胞内ＡＤＭ的浓度，降低该细胞对ＡＤＭ的ＩＣ５０，使该细胞对ＡＤＭ的抗性有数倍逆转．上述结果提示，ＰＩＣ－ＢＥ不仅是一种有效的广谱抗肿瘤剂。The effect of PIC BE,a kind of water soluble derivative of β elemene,on inhibition of cell growth,induction of apoptosis and multidrug resistance(MDR)in a human erythroleukemia cell variant K562/ADM was observed by means of typanblue assay,tetrazolium salt(MTT)assay,Hoechst 33 342 and propidium iodine(PI)fluorescence test,flow cytometry and fluorescence spectrophotometer.The results showed:(1)K562/ADM cell line was more 40 fold resistant to ADM than their sensitive counterparts(K562 cell line),but the IC 50 value of both cell lines to PIC BE was nearly no difference(17 88±0 80 and 19 13 ±0 09 μg/ml,respectively)( P >0 05);(2)In K562/ADM cell line,PIC BE(10 0～30 0 μ g/ml)could inhibit their growth and induce their apoptosis effectively( P <0 05 or P <0 01),and the effect was dose and time dependent within limited range;(3)Low cytotoxic dose(10 0 μg/ml)of PIC BE in combination with ADM(4 0 μg/ml)could enhance the effect of ADM on inhibition of cell growth and induction of apoptosis in K562/ADM cell line,increase the intracellular ADM concentration( P <0 05 or P <0 01),decline IC 50 value of K562/ADM cell line to ADM by more 2 5 fold than the control.These results suggest that PIC BE might be a effective anti tumor drug as well as a effective drug for reversal of MDR.

关 键 词：细胞凋亡 多药耐药性 β榄香烯吗素 红白血病 

分 类 号：R979.1[医药卫生—药品] R969.4[医药卫生—药学]