氯喹靶向溶酶体增加非小细胞肺癌A549细胞对紫杉醇的敏感性

摘要

O b jectnve: To investigate whether chloroquine, a taiget lysosone diug chenosensitizes non-snail cell lung cancer A549 cells to paclitaxel M e1hods: Lysosonal changes induced by paclitaxel and chbioquine in A549 cells were assayed by fluorescence staining with Lyso-TrackerRed DND-99 , and the viability ofA549 cells treated with paclitaxel and chbioquine canbinatbnwas detemined byusingMTT assay Results; A549 cells treatedwith paclitaxel displayed greatntmber of red fluorescence vesicleswith punctate foci in the cytoplaail ButA549 cells treatedwith chloioquhe or the conbination of paclitaxel and chbioquine displayed a decreased nunberof red fluorescence vesicles and diffuse fluorescence staining in these vesicles Chloioquine substantially increased ly-sosonal volume Chloioquine addition significantly decreased JC50 values of paclitaxel for A549 cells fian 6. 815μmo/ L to 2. eilLLmo/L, Chbioquine potentiated the growth inhibition of paclitaxel on A549. Conciisbn; Chloioquine taigeting lysosone significantly chenosensitizes A549 cells to paclitaxel%目的:探讨靶向溶酶体药物氯喹对非小细胞肺癌A549细胞对紫杉醇的化疗敏感性的影响.方法:以紫杉醇及氯喹作用于A549细胞,Lyso-Tracker Red DND-99进行细胞内溶酶体染色,采用荧光显微镜观察细胞内溶酶体变化,应用MTT比色法比较药物对A549细胞的生长抑制作用.结果:在紫杉醇作用的A549细胞浆内可观察到大量的点灶状红色荧光囊泡,而在氯喹及联合紫杉醇作用后红色荧光囊泡数量显著减少并伴囊泡体积增大及囊泡内弥散荧光染色,氯喹使得紫杉醇对A549细胞的IC50从6.815μmol/L下降至2.611μmol/L,氯喹显著提高紫杉醇对A549细胞的生长抑制作用.结论:氯喹靶向溶酶体提高A549细胞对紫杉醇的化疗敏感性.