摘要
目的:研究过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对人乳腺癌细胞MDA-MB-231体外生长影响,以评价其在人乳腺癌治疗上的应用潜力.方法:噻唑蓝(MTT)法检测罗格列酮对MDA-MB-231细胞体外生长抑制作用;应用PPARγ拮抗剂GW9662,分析罗格列酮对MDA-MB-231细胞增殖影响与PPARγ受体关系;流式细胞仪分析细胞周期,Annexin V-FITC和TUNEL法检测细胞凋亡.结果:罗格列酮干预下MDA-MB-231细胞G0/G1期比例上升,而S期比例下降,呈量-效关系抑制其生长,IC50=5.2μmol/L.PPARγ拮抗剂GW9662可部分逆转罗格列酮对MDA-MB-231细胞增殖抑制作用(P<0.05);100μmol/L罗格列酮还可诱导MDA-MB-231细胞凋亡,TUNEL法检测的凋亡率(18.4±3.1)%与Annexin V-FITC法检测的结果一致[(16.6±2.7)%](P>0.05).结论:罗格列酮通过PPARγ介导,使MDA-MB-231细胞G1期阻滞而抑制其增殖,高浓度时还可诱导其发生凋亡,罗格列酮有望成为治疗乳腺癌的有效药物.
AIM： To study the antitumor effects of peroxisome proliferator-activated receptor gamma （PPARγ） agonist rosiglitazone on human breast cancer cell line MDA-MB-231 and evaluate its underlying application value for breast cancer therapy. METHODS： MTY assay was used to observe cytostatic effects of rosiglitazone on MDA-MB-231 cells. PPARγ, antagonist GW9662 was used to analyze the influence of rosiglitazone on the proliferation of MDA-MB-231 cells as well as its relationship to PPARγ. The cell cycle distribution pattern was detected by flow cytometer. Apoptotic cells were determined both by Annexin V staining and TUNEL assay. RESULTS： MTY analysis demonstrated that rosiglitazone inhibited the growth of MDA-MB-231cells in a dosedependent manner, with ICs0 being 5.2 μmol/L. PPARγ antagonist GW9662 （5 μmol/L ） could, at least in part, reverse the inhibitory effects of rosiglitazone on the proliferation of MDA-MB- 231 ceils. Cell cycle analysis showed that, with the increasing concentration of rosiglitazone treatment, the percentage of G0/G1 phase cells increased while S phase cells decreased accordingly. Apoptotic effects by rosiglitazone showed that 100 μmol/L rosiglitazone could result in cell apeptosis detected by TUNEL, and the apoptotsis rate was （ 18.4 ± 3.1 ） %, much the same as compared to Annexin V assay by flow cytometry [ （ 16.6 ± 2.7 ） % ] （ P 〉 0.05）. CONCLUSION： Rosiglitazone treatment can inhibit the growth of MDA-MB-231 cell via PPARγ by inducing G0/G1 arrest and high dose administration of rosiglitazone can also induce the apoptosis of MDA-MB-231 cells, suggesting that PPARγ represents a putative molecular target for chemopreventive therapy and its agonist rosiglitazone might be an effective agent for the treatment of breast cancer.
出处
《第四军医大学学报》
北大核心
2007年第11期971-974,共4页
Journal of the Fourth Military Medical University
基金
国家自然科学基金(30572353)
