Department of General Practice, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, Jiangsu, China.
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Changzhou, 213000, Jiangsu, China.
Curr Mol Med. 2024;24(7):931-939. doi: 10.2174/1566524023666230801124826.
Semaphorin3A (Sema3a) is lowly expressed in the peripheral blood of gastric cancer patients, suggesting Sema3a may be involved in the progression of gastric cancer. Nevertheless, the specific role and the potential regulatory mechanism of Sema3a in gastric cancer is still obscure. Neuropilin-1 (NRP-1) has been reported to interact with Sema3a; herein, we intended to reveal the role and regulatory mechanism of Sema3a/neuropilin-1 (NRP-1) in gastric cancer progression.
Cell transfection was carried out to regulate gene expression. CCK-8 and colony formation assays were applied to estimate cell proliferation. Scratch assay and transwell assay were conducted to assess the cell migration and invasion abilities. Angiogenesis ability was assessed using a tubule-forming assay. The expression of corresponding genes and proteins were detected by RT-qPCR and western blot, respectively.
Data showed that Sema3a was downregulated in gastric cancer cells and NRP-1 was upregulated. Sema3a overexpression repressed NRP-1 level in AGS cells. Overexpression of Sema3a inhibited cell proliferation, migration, and invasion abilities as well as epithelial-mesenchymal transition (EMT) of AGS cells. Overexpression of Sema3a inhibited tube formation and reduced the expression of VEGFA/VEGFR2 in AGS cells. However, the effects of Sema3a overexpression on the malignant behaviors in AGS cells were partly reversed by NRP-1 overexpression. Additionally, Sema3a overexpression enhanced the inhibitory effects of Ramucirumab, an anti-VEGFR2 agent, on the proliferative, migratory, and invasive capabilities as well as EMT in AGS cells.
In conclusion, Sema3a alleviates the proliferation, migration, invasion, and angiogenesis capabilities of gastric cancer cells via repressing NRP-1. This finding may provide potential targets for gastric cancer therapy.
Semaphorin3A（Sema3a）在胃癌患者的外周血中低表达，表明 Sema3a 可能参与胃癌的进展。然而，Sema3a 在胃癌中的具体作用和潜在调节机制仍不清楚。神经纤毛蛋白-1（NRP-1）已被报道与 Sema3a 相互作用；在此，我们旨在揭示 Sema3a/神经纤毛蛋白-1（NRP-1）在胃癌进展中的作用和调节机制。
通过细胞转染来调节基因表达。使用 CCK-8 和集落形成实验来评估细胞增殖。划痕实验和 Transwell 实验用于评估细胞迁移和侵袭能力。管形成实验用于评估血管生成能力。通过 RT-qPCR 和 Western blot 分别检测相应基因和蛋白的表达。
数据表明 Sema3a 在胃癌细胞中下调，NRP-1 上调。Sema3a 的过表达抑制了 AGS 细胞中的 NRP-1 水平。Sema3a 的过表达抑制了 AGS 细胞的增殖、迁移和侵袭能力以及上皮-间充质转化（EMT）。Sema3a 的过表达抑制了 AGS 细胞的管形成，并降低了 VEGFA/VEGFR2 的表达。然而，NRP-1 的过表达部分逆转了 Sema3a 过表达对 AGS 细胞恶性行为的影响。此外，Sema3a 的过表达增强了抗 VEGFR2 药物 Ramucirumab 对 AGS 细胞增殖、迁移和侵袭能力以及 EMT 的抑制作用。
总之，Sema3a 通过抑制 NRP-1 减轻了胃癌细胞的增殖、迁移、侵袭和血管生成能力。这一发现可能为胃癌治疗提供潜在的靶点。
