Jiang Hongsheng, Hu Lingbo, Wu Quanfeng, Zhang Bitao, Sun Jianhua, Li Xiaoying
Department of Gastrointestinal Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, Hubei, China.
Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, Hubei, China.
Evid Based Complement Alternat Med. 2022 Nov 21;2022:6356583. doi: 10.1155/2022/6356583. eCollection 2022.
Gastric carcinoma has a high incidence, accounting for approximately 6% of all cancers worldwide. The in vivo antitumor effect of sodium selenite on gastric carcinoma has been demonstrated. This study therefore aimed to further explore its targets in gastric cancer in vitro and elucidate its mechanism of action. The effects of inorganic sodium selenite (NaSeO) on apoptosis, proliferation, and invasion of gastric cancer cells were investigated, and the interaction between NaSeO and expression of long noncoding RNA homeobox B cluster antisense RNA 1 (HOXB-AS1) was investigated to elucidate the specific mechanism of action of selenium on gastric cancer cell proliferation through regulation of HOXB-AS1. NaSeO downregulated the expression of HOXB-AS1 in the human gastric cancer (HGC) cell lines, HGC-27, NCI-N87, and KATO III cells, while inhibiting their proliferation and invasion and inducing apoptosis. The upregulation of HOXB-AS1 produced the opposite results. NaSeO was used to stimulate HGC-27 cells, which caused HOXB-AS1 overexpression. The cell counting kit-8 (CCK-8) assay revealed a decrease in cell proliferation, while western blotting, flow cytometry, and transwell migration assays showed the expression of apoptosis-related (Bad, Bcl-2, and cleaved-caspase-3) and invasion-related (MMP2, E-cadherin, and N-cadherin) proteins, indicating increased apoptosis and decreased invasion. We therefore conclude that NaSeO inhibits the malignant progression of gastric cancer by downregulating the expression of HOXB-AS1 and thus could be used as a potential drug for its treatment.
胃癌发病率很高，约占全球所有癌症的6%。亚硒酸钠对胃癌的体内抗肿瘤作用已得到证实。因此，本研究旨在进一步探讨其在体外胃癌中的作用靶点，并阐明其作用机制。研究了无机亚硒酸钠（NaSeO）对胃癌细胞凋亡、增殖和侵袭的影响，并研究了NaSeO与长链非编码RNA同源盒B簇反义RNA 1（HOXB-AS1）表达之间的相互作用，以阐明硒通过调控HOXB-AS1对胃癌细胞增殖的具体作用机制。NaSeO下调了人胃癌（HGC）细胞系HGC-27、NCI-N87和KATO III细胞中HOXB-AS1的表达，同时抑制其增殖和侵袭并诱导凋亡。HOXB-AS1的上调产生了相反的结果。用NaSeO刺激HGC-27细胞，导致HOXB-AS1过表达。细胞计数试剂盒-8（CCK-8）检测显示细胞增殖减少，而蛋白质免疫印迹法、流式细胞术和Transwell迁移检测显示凋亡相关蛋白（Bad、Bcl-2和裂解的半胱天冬酶-3）和侵袭相关蛋白（MMP2、E-钙黏蛋白和N-钙黏蛋白）的表达，表明凋亡增加且侵袭减少。因此，我们得出结论，NaSeO通过下调HOXB-AS1的表达来抑制胃癌的恶性进展，因此可作为其治疗的潜在药物。
