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Abstract：
OBJECTIVE: Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer.
METHODS: CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry.
RESULTS: CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway.
CONCLUSIONS: These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.
METHODS: CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry.
RESULTS: CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway.
CONCLUSIONS: These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.
摘要：
目的:胱抑素SA(CST2)属于半胱氨酸蛋白酶抑制剂超家族。新兴的研究表明，CST2通常在各种癌症中失调。其在胃癌中的作用和分子机制仍未得到充分研究。本研究旨在探讨CST2在胃癌中的表达及功能。
方法：通过Westernblot分析和验证CST2的表达。慢病毒在GC细胞中诱导CST2过表达，并评估了CST2表达水平与下游信号通路之间的相关性。此外,多种检测,包括细胞增殖，菌落形成,伤口愈合,和Transwell迁移/入侵，被认为是确定CST2过表达对胃癌的影响。流式细胞术检测细胞周期和细胞凋亡。
结果：在胃癌组织和细胞系中，蛋白质水平的CST2表达降低至降低，和CST2表达减弱胃癌的生长，作用仅限于胃癌细胞，在胃上皮GES-1细胞中不存在。此外，CST2被证明通过PI3K/AKT信号通路提高胃癌细胞对奥沙利铂的化学敏感性。
结论：这些发现表明CST2在胃癌组织和细胞系中在蛋白质水平上下调。此外,发现CST2通过PI3K/AKT信号通路减弱胃癌细胞的生长并增强对奥沙利铂的敏感性，特定于胃癌细胞系。CST2可能作为抑癌基因，增加胃癌对奥沙利铂的敏感性。
方法：通过Westernblot分析和验证CST2的表达。慢病毒在GC细胞中诱导CST2过表达，并评估了CST2表达水平与下游信号通路之间的相关性。此外,多种检测,包括细胞增殖，菌落形成,伤口愈合,和Transwell迁移/入侵，被认为是确定CST2过表达对胃癌的影响。流式细胞术检测细胞周期和细胞凋亡。
结果：在胃癌组织和细胞系中，蛋白质水平的CST2表达降低至降低，和CST2表达减弱胃癌的生长，作用仅限于胃癌细胞，在胃上皮GES-1细胞中不存在。此外，CST2被证明通过PI3K/AKT信号通路提高胃癌细胞对奥沙利铂的化学敏感性。
结论：这些发现表明CST2在胃癌组织和细胞系中在蛋白质水平上下调。此外,发现CST2通过PI3K/AKT信号通路减弱胃癌细胞的生长并增强对奥沙利铂的敏感性，特定于胃癌细胞系。CST2可能作为抑癌基因，增加胃癌对奥沙利铂的敏感性。
