PPARγ和RXRα的表达上调增强了对肿瘤细胞生长的抑制作用

Up-expression of peroxisome proliferator-activated receptor-γ and of retinoid X receptor-α enhances the inhibitory effect on tumor cells growth

目的研究过氧化物酶体增殖物活化受体γ(PPAPγ)和维甲类X受体α(RXRα)在人消化系统肿瘤(胃癌MGC803、结肠癌LOVO、肝癌SMMC7721)细胞中的表达及其对配体作用的反应。方法采用MTT检测细胞生长;半定量RT-PCR法检测PPARγ和RXRαmRNA的表达。结果吡格列酮(PGZ)单独作用及与9-顺式-维甲酸(9-cis-RA)联合作用72 h,对MGC803和SMMC7721产生较强的抑制作用,联合作用组的抑制作用显著强于PGZ单独作用组(P<0.01),但对LOVO的抑制作用不明显。PPARγ和RXRα在MGC803细胞中有较强表达,在SMMC7721和LOVO细胞中表达较弱。PGZ能显著上调MGC803和LOVO细胞中PPARγ的表达,联合作用组PPARγ表达比PGZ单独作用组显著升高(P<0.05);9-cis-RA能显著上调MGC803和LOVO细胞中RXRα的表达,联合作用组RXRα表达与9-cis-RA单独作用组无明显差别。结论在MGC803、LOVO和SMMC7721肿瘤细胞中,MGC803细胞PPARγ和RXRα表达最强,这对配体发挥作用可能是必需的,配体发挥的抑制细胞生长的效应可能与其介导的信号途径有关。

Objective To investigate the relationship between the expression of PPARγ and RXRα and the inhibitory effect of pioglizatone, ligand of PPARγ and 9-cis-RA, ligand of RXRα on growth of human digestive carcinoma cell lines （MGC803, LOVO and SMMC7721 ） in vitro. Methods The Antiproliferative effect was evaluated by MTT assay. The mRNA expression of PPARγ and RXRα was semi-quantified by RT-PCR. Results The growth of MGC803 and SMMC7721 cells was significantly inhibited when treated with PGZ and a combination of PGZ and 9-cis-RA, respectively, but no significant inhibitory effect was observed in LOVO cells. The combination group showed more inhibitory effect in MGC803 and SMMC7721 cells than PGZ alone （ P 〈 0.01 ）. PPARγ and RXRα mRNA were both expressed in MGC803 ,SMMC7721 and LOVO cells ,and the expressive level ranked in following order：MGC803 〉 SMMC7721 〉 LOVO. PGZ significantly up-regulates the expression of PPARγ in MGC803 and LOVO eels , the expression of PPARγ was higher in combination group than PGZ alone （P 〈0. 05）. The expression of RXRα in MGC803 and LOVO cells treated with 9-cis-RA were all significantly up-regulated, but no significant difference between combination group and 9-cis-RA alone was found. Conclusion The expression of PPARγ and RXRα in MGC803, SMMC7721 and LOVO cell lines predicts them response to pioglizatone and 9-cisretinoic acid treatment, the inhibitory effect is different in these three kinds of cell lines, it may be related to ligands-mediated signal pathway.