Li Hong-Xing, Zhao Wei, Shi Yan, Li Ya-Na, Zhang Lian-Shuang, Zhang Hong-Qin, Wang Dong
Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
Tumour Biol. 2015 Nov;36(11):8671-8. doi: 10.1007/s13277-015-3534-8. Epub 2015 Jun 6.
Small cell lung cancer (SCLC) accounts for 12 to 16% of lung neoplasms and has a high rate of metastasis. The present study demonstrates the antiproliferative effect of retinoic acid amide in vitro and in vivo against human lung cancer cells. The results from MTT assay showed a significant growth inhibition of six tested lung cancer cell lines and inhibition of clonogenic growth at 30 μM. Retinoic acid amide also leads to G2/M-phase cell cycle arrest and apoptosis of lung cancer cells. It caused inhibition of JAK2, STAT3, and STAT5, increased the level of p21WAF1, and decreased cyclin A, cyclin B1, and Bcl-XL expression. Retinoic acid amide exhibited a synergistic effect on antiproliferative effects of methotrexate in lung cancer cells. In lung tumor xenografts, the tumor volume was decreased by 82.4% compared to controls. The retinoic acid amide-treated tumors showed inhibition of JAK2/STAT3 activation and Bcl-XL expression. There was also increase in expression of caspase-3 and caspase-9 in tumors on treatment with retinoic acid amide. Thus, retinoic acid amide exhibits promising antiproliferative effects against human lung cancer cells in vitro and in vivo and enhances the antiproliferative effect of methotrexate.
小细胞肺癌（SCLC）占肺部肿瘤的12%至16%，且转移率很高。本研究证明了视黄酸酰胺在体外和体内对人肺癌细胞的抗增殖作用。MTT试验结果显示，在30μM浓度下，六种受试肺癌细胞系的生长受到显著抑制，集落形成生长也受到抑制。视黄酸酰胺还导致肺癌细胞的G2/M期细胞周期阻滞和凋亡。它抑制了JAK2、STAT3和STAT5，增加了p21WAF1的水平，并降低了细胞周期蛋白A、细胞周期蛋白B1和Bcl-XL的表达。视黄酸酰胺对甲氨蝶呤在肺癌细胞中的抗增殖作用表现出协同效应。在肺癌异种移植模型中，与对照组相比，肿瘤体积减少了82.4%。经视黄酸酰胺处理的肿瘤显示JAK2/STAT3激活和Bcl-XL表达受到抑制。在用视黄酸酰胺治疗的肿瘤中，caspase-3和caspase-9的表达也有所增加。因此，视黄酸酰胺在体外和体内对人肺癌细胞均表现出有前景的抗增殖作用，并增强了甲氨蝶呤的抗增殖作用。
