Liu Yan, Bi Tingting, Yuan Fukang, Gao Xinbao, Jia Gaolei, Tian Zhilong
Department of Surgery for Vascular Thyroid and Hernia, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China.
Department of Gastroenterology, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2507-2515. doi: 10.1007/s00210-020-01858-6. Epub 2020 Mar 26.
S-adenosylmethionine (SAM) is a naturally occurring physiologic molecule found ubiquitously in all mammalian cells and an essential compound in many metabolic pathways. It has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, the precise molecular mechanism involved in its anticancer effect is not yet clear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of SAM on human gallbladder cancer cells (GBC-SD and SGC-996) in vitro and in vivo. Cells were dealt with SAM and subjected to cell viability, colony formation, Hoechst staining, apoptosis, cycle arrest, western blot, and xenograft tumorigenicity assay. Experimental results showed that SAM could significantly inhibit the growth and proliferation and induce the apoptosis as well as cell cycle arrest in G0/G1 phase of GBC-SD and SGC-996 cells in a dose-dependent manner in vitro. The expression levels of p-JAK2, p-STAT3, Mcl-1, and Bcl-XL were significantly downregulated. In addition, inhibition of the JAK2/STAT3 pathway significantly enhanced the anti-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. More importantly, our in vivo studies demonstrated that administration of SAM could significantly decrease the tumor weight and volume and immunohistochemistry analysis proved the downregulation of p-JAK2 and p-STAT3 in tumor tissues following SAM treatment, consistent with our in vitro results. In summary, our findings indicated that SAM can inhibit cell proliferation and induce apoptosis as well as cycle arrest of GBC cells by suppression of JAK2/STAT3 pathways and the dramatic effects of SAM hinting that SAM might be a useful therapeutic option for patients suffering from gallbladder cancer.
S-腺苷甲硫氨酸（SAM）是一种天然存在的生理分子，普遍存在于所有哺乳动物细胞中，是许多代谢途径中的必需化合物。据报道，它具有许多药理特性，包括防癌和抗癌作用。然而，其抗癌作用的确切分子机制尚不清楚。本研究旨在探讨SAM在体外和体内对人胆囊癌细胞（GBC-SD和SGC-996）的抗癌活性及其潜在机制。用SAM处理细胞，并进行细胞活力、集落形成、Hoechst染色、凋亡、细胞周期阻滞、蛋白质印迹和异种移植致瘤性测定。实验结果表明，在体外，SAM能以剂量依赖性方式显著抑制GBC-SD和SGC-996细胞的生长和增殖，诱导其凋亡以及使细胞周期阻滞在G0/G1期。p-JAK2、p-STAT3、Mcl-1和Bcl-XL的表达水平显著下调。此外，抑制JAK2/STAT3途径显著增强了SAM的抗凋亡作用，表明JAK2/STAT3在该过程中起关键作用。更重要的是，可以显著降低肿瘤重量和体积，免疫组织化学分析证明SAM处理后肿瘤组织中p-JAK2和p-STAT3下调，这与我们的体外结果一致。总之，我们的研究结果表明，SAM可以通过抑制JAK2/STAT3途径抑制胆囊癌细胞的增殖，诱导其凋亡和细胞周期阻滞，SAM的显著作用表明它可能是胆囊癌患者的一种有用的治疗选择。
