背景:结直肠癌(CRC)是一种常见的恶性肿瘤,具有很高的发病率和死亡率。先前的研究已经证明白细胞介素(IL)-22参与CRC进展;然而,确切的机制尚不清楚。本研究旨在探讨IL-22对CRC细胞增殖和转移的影响。
方法:采用酶联免疫吸附试验(ELISA)检测CRC患者血清和组织中IL-22的水平。细胞计数试剂盒-8(CCK-8)测定用于检测用不同IL-22浓度处理的CRC(HCT116)细胞的活力。殖民地的形成,Transwell入侵,和划痕试验用于评估IL-22对细胞增殖的影响,入侵,和移民。进行蛋白质印迹以测量磷脂酰肌醇3-激酶(PI3K)的表达水平,蛋白激酶B(AKT),p-PI3K,p-AKT,E-cadherin,用IL-22或PI3K抑制剂处理的HCT116细胞中的基质金属蛋白酶(MMP)-2,MMP-9,SNAI1和TWIST1。
结果:ELISA结果显示,与对照组相比,CRC患者血清和组织中IL-22的表达明显增加。IL-22处理以浓度依赖性方式增加细胞活力和集落形成,并增强细胞侵袭和迁移。Western印迹分析显示IL-22刺激上调p-PI3K和p-AKT表达,而PI3K和AKT总水平保持不变。此外,IL-22还降低了E-cadherin的表达,并增加了MMP-2,MMP-9,SNAI1和TWIST1的表达。
结论:IL-22激活PI3K-AKT通路,促进HCT116细胞增殖和转移。靶向PI3K/AKT途径的调节可能是CRC的潜在治疗策略。
BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality rates. Previous studies have demonstrated that interleukin (IL)-22 is involved in CRC progression; however, the exact mechanism remains unclear. This study aimed to investigate the effects of IL-22 on CRC cell proliferation and metastasis.
METHODS: IL-22 levels in the serum and tissues of CRC patients were measured using enzyme-linked immunosorbent assay (ELISA). Cell counting kit-8 (CCK-8) assay was used to detect the viability of CRC (HCT116) cells treated with different IL-22 concentrations. Colony formation, Transwell invasion, and scratch assays were employed to assess the effects of IL-22 on cell proliferation, invasion, and migration. Western blotting was performed to measure the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), p-PI3K, p-AKT, E-cadherin, matrix metalloproteinase (MMP)-2, MMP-9, SNAI1, and TWIST1 in HCT116 cells treated with IL-22 or a PI3K inhibitor.
RESULTS: ELISA results showed that the expression of IL-22 was significantly increased in the serum and tissues of CRC patients compared to controls. IL-22 treatment increased cell viability and colony formation in a concentration-dependent manner and enhanced cell invasion and migration. Western blotting analysis revealed that IL-22 stimulation upregulated p-PI3K and p-AKT expression, while total PI3K and AKT levels remained unchanged. Additionally, IL-22 also decreased E-cadherin expression and increased the expression of MMP-2, MMP-9, SNAI1, and TWIST1.
CONCLUSIONS: IL-22 activates the PI3K-AKT pathway and promotes HCT116 cell proliferation and metastasis. Targeting the regulation of the PI3K/AKT pathway may be a potential therapeutic strategy for CRC.