Zhang Sumei, Shi Rui, Chen Shaolong, Wei Xiang, Zhou Qing, Wang Yuan
Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Gene Research of Anhui, Hefei, Anhui 230032, P.R. China.
Clincal Center of Tumor Therapy, The Lu'an People's Hospital, Lu'an, Anhui 237005, P.R. China.
Oncol Lett. 2018 Feb;15(2):1523-1528. doi: 10.3892/ol.2017.7499. Epub 2017 Nov 29.
Caveolin-1 is a scaffold protein of caveolae in the mucosa of the gastrointestinal tract and acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. Caveolin-1 stabilizes cell-cell and cell-matrix contacts and is a hallmark of a number of different types of human cancer, including gastric cancer. All-trans retinoic acid (ATRA), a derivative of vitamin A, has been demonstrated to exhibit tumor inhibitory effects in acute leukemia and certain types of solid tumor. In the present study, treatment with ATRA was demonstrated to inhibit the proliferation of gastric cancer cell line SGC7901, in a time- and dose-dependent manner. The markedly increased membrane localization of caveolin-1 was observed in the cells that were treated with 10 µmol/l ATRA for > 48 h. In addition, it was observed that treatment with ATRA was able to regulate the level of phosphorylation of extracellular signal-regulated kinase (ERK). Therefore, the SGC7901 cells were treated with a specific agonist of ERK/mitogen-activated protein kinase (MAPK) investigate whether ATRA mediated its effects via the ERK/MAPK signaling pathway. The results of the present study demonstrated that ATRA-induced increase in membrane localization of caveolin-1 was reversed by treatment with a specific agonist of ERK/MAPK. Together, these results suggest that ATRA exhibits anti-gastric cancer effects. ATRA may regulate the membrane localization of caveolin-1 in order to inhibit the proliferation of SGC7901 cells. These effects of ATRA may be mediated by inhibiting the activation of ERK/MAPK signaling pathway. These results contribute to the current knowledge on the potential use of ATRA as therapy for solid tumors and provide further insight into the potential molecular mechanisms of ATRA action.
小窝蛋白-1是胃肠道黏膜中小窝的一种支架蛋白，通过与细胞黏附分子和信号受体相互作用而作为一种肿瘤调节因子。小窝蛋白-1可稳定细胞间和细胞与基质的接触，是包括胃癌在内的多种不同类型人类癌症的一个标志。全反式维甲酸（ATRA）是维生素A的衍生物，已被证明在急性白血病和某些类型的实体瘤中具有肿瘤抑制作用。在本研究中，已证明用ATRA处理可抑制胃癌细胞系SGC7901的增殖，呈时间和剂量依赖性。在用10 μmol/l ATRA处理超过48小时的细胞中，观察到小窝蛋白-1的膜定位明显增加。此外，观察到用ATRA处理能够调节细胞外信号调节激酶（ERK）的磷酸化水平。因此，用ERK/丝裂原活化蛋白激酶（MAPK）的特异性激动剂处理SGC7901细胞，以研究ATRA是否通过ERK/MAPK信号通路介导其作用。本研究结果表明，用ERK/MAPK的特异性激动剂处理可逆转ATRA诱导的小窝蛋白-1膜定位增加。总之，这些结果表明ATRA具有抗胃癌作用。ATRA可能调节小窝蛋白-1的膜定位以抑制SGC7901细胞的增殖。ATRA的这些作用可能是通过抑制ERK/MAPK信号通路的激活来介导的。这些结果有助于当前关于ATRA作为实体瘤治疗潜在用途的知识，并为ATRA作用的潜在分子机制提供了进一步的见解。
