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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
Chloroquine Targeting Lysosome Chemosensitizes Non-small Cell Lung Cancer A549 Cells to Paclitaxel
【摘要】 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。
【Abstract】 Objective:To investigate whether chloroquine,a target lysosome drug,chemosensitizes non-small cell lung cancer A549 cells to paclitaxel.Methods:Lysosomal changes induced by paclitaxel and chloroquine in A549 cells were assayed by fluorescence staining with Lyso-Tracker Red DND-99,and the viability of A549 cells treated with paclitaxel and chloroquine combination was determined by using MTT assay.Results:A549 cells treated with paclitaxel displayed great number of red fluorescence vesicles with punctate foci in the cytoplasm.But A549 cells treated with chloroquine or the combination of paclitaxel and chloroquine displayed a decreased number of red fluorescence vesicles and diffuse fluorescence staining in these vesicles.Chloroquine substantially increased lysosomal volume.Chloroquine addition significantly decreased IC50values of paclitaxel for A549 cells from 6.815μmol/L to 2.611μmol/L,Chloroquine potentiated the growth inhibition of paclitaxel on A549.Conclusion:Chloroquine targeting lysosome significantly chemosensitizes A549 cells to paclitaxel.
【Key words】 Lysosome; Chloroquine; Paclitaxel; A549 Cells; Autophagy; NSCLC;
- 【文献出处】 肿瘤预防与治疗 ,Journal of Cancer Control and Treatment , 编辑部邮箱 ,2011年06期
- 【分类号】R734.2
- 【被引频次】5
- 【下载频次】161