title: Retinoic acid amide inhibits JAK/STAT pathway in lung cancer which leads to apoptosis.
abstract: 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.
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
authors.forename: Ya-Na
authors.initials: YN
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
authors.forename: Lian-Shuang
authors.initials: LS
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.
authors.forename: Hong-Qin
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China. wangdong547@gmail.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D050791:STAT Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000577:Amides; D009363:Neoplasm Proteins; D050791:STAT Transcription Factors; D014212:Tretinoin
keywords: Antiproliferative; Dimerization; Lung cancer; Metastasis; Methotrexate; STAT3