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作 者:陈莎[1] 韩起[1] 王旭辉[2] 杨明珍[1] 张竹君[1] 陈安[1] 胡川闽 李淑慧[1]
机构地区:[1]中国人民解放军第三军医大学,重庆400038 [2]中国人民解放军第三军医大学大坪医院野战外科研究所,重庆400042
出 处:《时珍国医国药》2013年第3期516-519,共4页Lishizhen Medicine and Materia Medica Research
基 金:国家自然科学基金(No.81272909)
摘 要:目的观察调节自噬对乳腺癌细胞紫杉醇耐药性的影响。方法选取两株乳腺癌细胞MDA-MB-231及MDA-MB-468细胞,分为不同浓度的紫杉醇(PTX)组、联合自噬激动剂雷帕霉素(PTX+Rapa)组和联合自噬抑制剂3-MA(PTX+3-MA)组(对照组给予相应溶剂),分别作用24 h、48 h及72 h后,应用MTT比色法检测各组细胞的存活率及抑制率。结果 PTX+Rapa组对两株乳腺癌细胞的抑制作用均显著优于单独给药的PTX组及PTX+3-MA给药组(P<0.01),而PTX+3-MA组对两株乳腺癌细胞的抑制作用则明显弱于单独给药的PTX组(MDA-MB-231,P<0.05;MDA-MB-468,P<0.01),提示自噬激动剂雷帕霉素(10 nm)可降低乳腺癌细胞对紫杉醇耐药性,增强紫杉醇对乳腺癌细胞的抑制作用,而自噬抑制剂3-MA(10 mm)在一定程度上增强乳腺癌细胞紫杉醇耐药性,拮抗紫杉醇对乳腺癌细胞的抑制作用。结论调节自噬能明显影响乳腺癌细胞对紫杉醇的耐药性,这为自噬与乳腺癌细胞紫杉醇耐药性关系的研究提供了新的思路。Objective To observe the effects of regulated autophagy in the resistance of breast cancer cells to Paclitaxel.Methods Breast cancer cells lines:MDA-MB-231 and MDA-MB-468 were treated with PTX alone or PTX combination with Rapamycin or PTX combination with 3-MA for 24,48,72h.MTT method test was used to determine the proliferative inhibition rate and survival rate of treated cells.Results The survival rate of treated cells in the PTX combination with Rapamycin group was better than that of PTX alone or PTX combination with 3-MA group(P0.01).The survival rate of treated cells in the PTX combination with 3-MA group was weaker than that of PTX alone.(MDA-MB-231,P0.05;MDA-MB-468,P0.01).It indicated that the Rapamycin(autophagy agonist) can reduce the resistance of breast cancer cells to paclitaxel and enhance the inhibitory effects of paclitaxel.But the 3-MA(autophagy inhibitor) otherwise improved the resistance of breast cancer cells to paclitaxel to some extent and protected cells from paclitaxel-induced cell death.Conclusion The regulation of autophagy makes a notable contribution in the resistance of breast cancer cells to paclitaxel,which may provide a new possibility for the study in breast cancer treatment.
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