共轭三烯酸对乳腺癌细胞的增殖抑制和凋亡诱导作用  

The Proliferation Inhibition and Apoptosis Induction Effects of Conjugated Trienoic Fatty Acids for Breast Cancer Ceils

作　　者：张婷婷[1] 毛羽[2] 张全波[1] 高艳萍[1] 林苹[1] 张洁[1] 肖恒怡[1] 王修杰[1] 

机构地区：[1]四川大学华西医院,生物治疗国家重点实验室老年医学研究室,成都610041 [2]西南民族大学少数民族药物研究所,成都610041

出　　处：《肿瘤预防与治疗》2010年第1期10-14,22,共6页Journal of Cancer Control And Treatment

基　　金：四川省科技厅攻关项目(批准号:2008SG0016);四川省卫生厅科研课题(批准号:090316)资助

摘　　要：目的:探讨共轭三烯酸(TCLA)对乳腺癌细胞的增殖抑制、凋亡作用及其作用机制。方法:用TCLA处理人正常肝细胞(L02)及乳腺癌细胞(MCF-7),用细胞增殖试验(MTT法)、克隆形成试验、EdU掺入试验研究TCLA对人正常肝细胞和乳腺癌细胞的增殖抑制作用;吖啶橙/溴乙啶(AO/EB)染色检测细胞凋亡;流式细胞术检测TCLA对细胞周期的影响;RT-PCR检测凋亡相关基因PPAR-γ、P53、CASPASE-3 mRNA表达。结果:用TCLA处理后,肿瘤细胞增殖活性降低(P<0.05),半效抑制浓度(IC_(50))为50μmol,呈时问-剂量-效应关系;克隆形成下降(P<0.05)亦呈时间-剂量-效应关系;EdU标记指数降低(P<0.05),AO/EB染色凋亡细胞增多(P<0.05),细胞周期分布改变,凋亡指数显著增加(P<0.01),S期细胞显著减少(P<0.05);RT-PCR检测RTPCR检测凋亡相关基因PPAR-γ(P<0.05)、P53(P<0.05)、CASPASE-3(P<0.01)mRNA表达均比对照组显著增加。结论:TCLA对乳腺癌细胞具有抑制增殖和诱导凋亡作用,其作用机理可能与抑制DNA合成、细胞周期阻滞、上调凋亡相关基因PPARγ、P53、CASPASE-3表达有关。Objective： To investigate the growth inhibition and apoptosis induction effects of conjugated trienoic fatty acids （TCLA） for human breast cancer cells and to elucidate its mechanism. Methods： Human normal liver cells and breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, EdU incorporation, AO/ EB staining apoptotic cells, and cell cycle distribution through flow cytometry after treatment with TCLA. The expression of PPAR-3,, P53, CASPASE- 3 mRNA were detected using RT-PCR. Results： After TCLA treatment, the proliferation （ IC50 = 50μmol） and colony formation of cancer cells decreased （ P 〈 0. 05 ） ; EdU labeling index of cancer cells decreased （ P 〈 0.05 ） ; and AO/EB stained apoptotic cells increased （ P 〈 0. 05 ）. The apoptotic index increased（P 〈 0.01 ）, and the cells in S phase decreased（ P 〈 0.01 ）by FCM analvsis. RT -RCR showed that TCLA significantly increased the expression level of PPAR-γ,P53, and CASPASE-3 mRNA. Conclusion： The findings in this experimental study suggest that TCLA exhibits a potential cytotoxicity and apoptosis induction to human breast cancer cells. And the mechanism of these actions might be associated with the inhibition of DNA synthesis, the induction of apoptosis, cell cycle arrest and up-regulation of PPAR-3,, P53, CASPASE- 3 expressions in cancer ceils.

关 键 词：共轭三烯酸 乳腺癌细胞 增殖抑制 凋亡诱导 

分 类 号：R737.9[医药卫生—肿瘤]