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目的: 观察氧化酶体激活物增殖受体( PPAR??) 激动剂罗格列酮( ROZ) 在体外激活PPAR?? 后对MCF- 7 细胞的生长抑制及诱导凋亡作用。方法:MTT 法检测ROZ 对MCF- 7 细胞的生长抑制作用; 集落形成实验观察ROZ 对MCF- 7 细胞集落形成的影响; 不同浓度ROZ 作用72h, Hoechst33342 染色观察MCF- 7 细胞的形态变化, 流式细胞光度分析术( FCM) 检测凋亡细胞百分率以及ROZ 对细胞周期的影响; Western blot 方法检测ROZ 对MCF- 7 细胞Bcl- 2、Caspase- 3 表达的影响。结果: ROZ 可呈剂量依赖性抑制MCF- 7 细胞的生长及集落形成。ROZ 浓度为6 ?? 10- 5M 和3 ?? 10- 4M 时则G1 期细胞数明显增加, S 期相应减少。 Hoechst33342 染色经ROZ 处理的肿瘤细胞染色质呈颗粒状, 且有凋亡小体出现。FCM 检测结果显示, ROZ 作用72h 凋亡细胞数达 22. 05%。Western blot 提示ROZ 可抑制Bcl- 2 表达, 促进Caspase3 表达。结论: ROZ 在体外可抑制MCF- 7 细胞的增殖并诱导其凋亡, 这可能与其抑制Bcl- 2 表达、促进caspase3 表达有关。提示ROZ 有望成为乳腺癌治疗药或肿瘤治疗的辅助用药, PPAR?? 有潜力成为肿瘤治疗的新靶点。

英文摘要:

Objective: To observe the effects of rosiglitazone( ROZ) , a perox isome proliferator- activated receptor- ?? activation, in the inhibition of tumor growth and inducement apoptosis in breast cancer in vitro. Methods: MTT was used to detect how ROZ inhibited the growth of MCF- 7, observing ROZ how to influence the colony formation of MCF- 7 by colony formation test. After different concentration of ROZ for 72 hours, the morphologic change ofMCF- 7 was seen by Hoechst33342 dyeing; the apoptosis percentage and cell cycle change were detected by FCM; the effects of ROZ in the expression of Bcl- 2 and Caspase- 3 of MCF- 7 were evaluated by Western Blotting. Results: Using ROZ to treat breast cancer, with a dose- dependence, could inhibit cell growth and colony formation of MCF- 7. The number of cells in G1 phase increased and the number of cells in S phase decreased when the concentration of ROZ was 6?? 10- 5M and 3?? 10- 4M. Through Hoechst33342 dyeing, there were granulochromatin and apoptotic body in tumor cells after being treated with ROZ for 72 hours, and the number of apoptosis cell reached 22. 05% by FCM. ROZ inhibited the expression of Bcl- 2 and enhanced the expression of Caspase- 3. Conclusion: ROZ inhibited the cell proliferation and induced apoptosis in vitro, which may be relative to inhibiting the expression of Bcl- 2 and enhancing the expression of Caspase- 3. These results hint that ROZ is hoped to be the therapeutic drug or aid drug in tumor treatment. PPAR?? has great potentialities to be new target of tumor treatment.

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