Hydrogen gas inhibits lung cancer progression through targeting SMC3
Hydrogen gas inhibits lung cancer progression through targeting SMC3
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DOI：
10.1016/j.biopha.2018.05.055
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发表时间：
2018-08-01
影响因子：
7.5
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Wang, Dongchang;Wang, Lifei;Chen, Gang
肺癌是地球仪上最常见的致死性恶性肿瘤之一。由于其高转移潜能和耐药性，患者的肿瘤是暗淡的。因此，在本研究中，我们的目标是找到一种更有效的治疗肺癌的方法。本研究采用CCK-8、流式细胞术、创伤愈合实验和transwell实验分别研究了氢气（H-2）对肺癌细胞株A549和H1975细胞活力、凋亡、迁移和侵袭能力的影响。采用RNA-seq、qPCR和western blotting方法检测H-2组与对照组之间的差异表达基因（DEG），寻找与染色体浓缩相关的基因。此外，我们证实了3号染色体（SMC 3）和H-2的结构维持对肺癌的进展在体外和体内。结果表明，H-2可抑制A549和H1975细胞的活力、迁移和侵袭能力，促进细胞凋亡，并可诱导细胞发生G2/M期阻滞。H-2下调NIBPL、SMC 3、SMC 5和SMC 6的表达，下调Cyclin D1、CDK 4和CDK 6的表达。在A549和H1975细胞中，H-2在细胞分裂过程中转移了SMC 3的亚细胞位置，降低了其稳定性，增加了其泛素化。此外，H-2对A549和H1975细胞增殖、迁移、侵袭的抑制作用和促进细胞凋亡的作用均被H-2过表达的SMC 3所消除。动物实验结果表明，H-2组肿瘤重量明显小于对照组，但大于顺铂组。H-2和顺铂均能降低Ki-67、VEGF和SMC 3的表达，以顺铂作用最明显。提示H-2可能通过下调SMC 3抑制肺癌的发生发展，为肺癌的治疗提供了新的思路。
Lung cancer is one of the most common lethal malignancies in the globe. The patients' prognoses are dim due to its high metastatic potential and drug resistance. Therefore, in the present study, we aim to find a more potent therapeutic approach for lung cancer. We mainly explored the function of hydrogen gas (H-2) on cell viability, apoptosis, migration and invasion in lung cancer cell lines A549 and H1975 by CCK-8, flow cytometry, wound healing and transwell assays, respectively. We used RNA-seq, qPCR and western blotting to detect the different expression genes (DEGs) between H-2 group and control group to find the gene related to chromosome condensation. Besides, we confirmed the structural maintenance of chromosomes 3 (SMC3) and H-2 on the progression of lung cancer in vitro and vivo. Results showed that H-2 inhibited cell viability, migration and invasion, and catalyzed cell apoptosis and H-2 induced A549 and H1975 cells G2/M arrest. Besides, H-2 down-regulated the expression of NIBPL, SMC3, SMC5 and SMC6, and also reduced the expression of Cyclin D1, CDK4 and CDK6. H-2 translocated the subcellular location of SMC3 during cell division and decreased its stability and increased its ubiquitination in both A549 and H1975 cells. In addition, inhibition of the proliferation, migration and invasion and promotion of the apoptosis of A549 and H1975 cells induced by H-2 were all abolished when overexpressed SMC3 in the presence of H-2. Animal experimental assay demonstrated that the tumor weight in H-2 group was significantly smaller than that in control group, but was bigger than cis-platinum group. The expression of Ki-67, VEGF and SMC3 were decreased when mice were treated with H-2 or cis-platinum, especially for cis-platinum. All data suggested that H-2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer.