Bacillus Calmette-Guérin induces the expression of peroxisome proliferator-activated receptor gamma in bladder cancer cells.
Bacillus Calmette-Guérin induces the expression of peroxisome proliferator-activated receptor gamma in bladder cancer cells.
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卡介苗诱导膀胱癌细胞中过氧化物酶体增殖物激活受体γ的表达。
DOI：
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发表时间：
2006
影响因子：
5.4
通讯作者：
A. Eiján
中科院分区：
文献类型：
--
作者：
C. Lodillinsky;María Sol Umerez;M. Jasnis;A. Casabé;E. Sandes;A. Eiján
卡介苗（BCG）被认为是治疗浅表性和原位膀胱癌最有效的治疗方法之一。 BCG 抗肿瘤活性的确切机制尚不完全清楚。过氧化物酶体增殖物激活受体γ (PPARgamma) 是配体激活转录因子核受体超家族的成员，参与细胞生长和分化以及炎症过程。 PPARgamma 在正常尿路上皮中表达，表达缺乏与膀胱癌进展相关。我们分析了 PPARgamma 是否参与 BCG 对膀胱癌细胞存活的抑制。采用免疫荧光和免疫组织化学技术评估小鼠 MB49 和人 T24 膀胱癌细胞中 PPARgamma 的表达。分别使用MTS和Griess试剂评价体外细胞活力和一氧化氮（NO）产生。我们的结果表明，BCG 在体外和体内诱导膀胱肿瘤细胞中 PPARgamma 的细胞质表达。 BADGE 是该受体的拮抗剂，可在体外消除 BCG 介导的细胞毒性。天然激动剂 15-脱氧-Delta12,14 前列腺素 J2 (15-d-PGJ2) 但不是合成激动剂罗格列酮 (RO)，可在体外诱导两种癌细胞系细胞活力的抑制，并且 BADGE 可以部分逆转该效应。我们还确定了 PPARgamma 的激活是否可以抑制 NO 的产生，NO 被认为是膀胱肿瘤细胞的生存因素。 15-d-PGJ2 和 RO 均通过 PPARgamma 独立途径显着抑制 T24 和 MB49 细胞中 NO 的产生，因为它不被 BADGE 拮抗。因此，我们的结果表明，BCG 在体内和体外诱导膀胱肿瘤细胞中的功能性 PPARγ，这些受体本质上参与了 BCG 的抗肿瘤活性。
Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial and in situ bladder cancer. The exact mechanism of the antitumor activity of BCG is not completely understood. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that is involved in cell growth and differentiation as well as inflammatory processes. PPARgamma is expressed in normal urothelium and a lack of expression was associated with bladder cancer progression. We analyzed whether PPARgamma is involved in the inhibition of bladder cancer cell survival by BCG. PPARgamma expression in murine MB49 and human T24 bladder cancer cells was evaluated employing immunofluorescence and immunohistochemistry techniques. In vitro cell viability and nitric oxide (NO) production was evaluated by using MTS and Griess reagent respectively. Our results show that BCG induced the cytoplasmatic expression of PPARgamma in bladder tumor cells in vitro and in vivo. BADGE, antagonist of this receptor, abrogated in vitro BCG-mediated cell cytotoxicity. Natural agonist 15-deoxy-Delta12,14 prostaglandin J2 (15-d-PGJ2) but not rosiglitazone (RO), a synthetic agonist, induced in vitro inhibition of cell viability of both cancer cell lines and the effect was partially reversed by BADGE. We also determined whether the activation of PPARgamma could inhibit NO production, which is considered a survival factor for bladder tumor cells. Both 15-d-PGJ2 and RO significantly inhibited the NO production in T24 and MB49 cells by PPARgamma-independent pathway since it was not antagonized by BADGE. Thus, our results show that BCG induces functional PPARgamma in bladder tumor cells in vivo and in vitro, being these receptors intrinsically involved in the antitumor activity of BCG.
影响因子：
6
作者：
Nakashiro, K;Hayashi, Y;Oyasu, R
通讯作者：
Oyasu, R
DOI：
10.1152/ajprenal.1997.273.6.f1013
发表时间：
1997-12-01
影响因子：
4.2
作者：
Guan, YF;Zhang, YH;Breyer, MD
通讯作者：
Breyer, MD