Peroxisome proliferator- activated receptor gamma inhibits liver cancer proliferation and metastasis in vitro
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摘要:
目的检测过氧化物酶体增殖物激活受体(PPAR)γ对肝癌的发生发展和侵袭转移的抑制作用。方法培养肝癌细胞MHCC97L,以携带PPARγ腺病毒(Ad-PPARγ)为载体使PPARγ在肝癌细胞内高表达,联合PPARγ激动剂罗格列酮治疗,运用MTS、流式细胞仪、细胞伤口愈合及基质胶侵袭试验检测PPARγ对肝癌细胞增殖、调亡和运动侵袭能力的影响。多个样本均数间的比较用单因素方差Bonferroni校正法分析。两组样本均数比较用t检验。结果相对于对照组,Ad-PPARγ使肝癌细胞高表达PPARγ,进而显著抑制细胞的增殖活力(P<0.01),诱导细胞凋亡(P<0.01),削弱细胞迁移和侵袭能力(下降20%60%)。AdPPARγ和罗格列酮对抑制肝癌细胞增长和转移具有联合效益。结论 PPARγ对肝癌细胞的增殖生长和侵袭转移有抑制作用,本研究为临床寻找可能的肝癌标志物和基因治疗提供了新思路和理论基础。
Abstract:Objective To investigate the inhibitory effect of peroxisome proliferator- activated receptor gamma ( PPARγ) on the development, progression, invasion, and metastasis of liver cancer cells. Methods Hepatocellular carcinoma ( HCC) MHCC97L cells were randomly assigned to be transfected with Ad- PPARγ or Ad- LacZ ( control) . The cells were also exposed to PPARγ agonist rosiglitazone. Cell proliferation, apoptosis, migration, and invasive ability were evaluated using MTS assay, flow cytometry, wound healing test, and transwell invasion assay. Multiple comparisons of means between groups were conducted using one- way analysis of variance with Bonferroni correction; the means of two groups were compared using the t test. Results Ad- PPARγ transfection resulted in higher expression of PPARγprotein in HCC cells compared with control cells, which suppressed cell proliferation ( P < 0. 01) , induced cell apoptosis ( P < 0. 01) , and suppressed cell migration and invasion. Moreover, the invasiveness of HCC cells transfected with Ad- PPARγ was reduced by 20% ~ 60%.Rosiglitazone enhanced the inhibitory effect of Ad- PPARγ on the growth and migration of HCC cells. Conclusion PPARγ exerts an inhibitory effect on the proliferative, invasive, and metastatic potential of HCC cells in vitro. This study sheds new light on the search for potential markers and gene therapies for liver cancer.
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Key words:
- PPAR gamma /
- carcinoma, hepatocellular /
- neoplasm invasiveness /
- apoptosis /
- cell proliferation
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