腺苷受体A1介导ω-3多不饱和脂肪酸诱导胃癌细胞凋亡的机制研究

Gastric cancer patients usually present the different degree of malnutrition, which affects the efficacy of treatment and prognosis. A safe, effective adjuvant therapy can improve the prognosis and quality of life of patients. Omega-3 polyunsaturated fatty acids (ω-3PUFAs) as a special nutrient, confirmed its anti-tumor effect in several researchs, our preliminary studies have found that ω-3PUFAs induce apoptosis of gastric cancer cells via ADORA1, but the exact molecular mechanism is unclear. This project aims to (1)detect the expression of ADORA1 in gastric cancer cell lines and tissues, for analysing the relationship between ADORA1 and clinical pathological characteristics of gastric cancer. (2) to study the effect of ADORA1 on the biological function of gastric cancer cells through the intervention of its expression and drugs targeting to block ADORA1, and further verified in nude mice model, for understand the effect of ω-3PUFAs on the growth of gastric cancer via ADORA1. And to investigate the molecular mechanism which ω-3PUFAs regulate the downstream signaling of ADORA1 and initiate apoptosis program. We clarify the mechanism that ω-3PUFAs exert a tumor suppressor action via ADORA1. The results provide a theoretical basis which ω-3 polyunsaturated fatty acids are applied in gastric cancer, as the adjuvant treatment.

胃癌患者大多存在不同程度的营养不良，严重影响了治疗效果及预后。安全、有效的辅助治疗能够改善患者预后及生活质量。ω-3多不饱和脂肪酸（ω-3PUFAs）作为一种特殊的营养素，其抗肿瘤的作用在许多研究中被发现。我们的前期研究发现ω-3PUFAs能够通过腺苷受体A1（ADORA1）诱导胃癌细胞的凋亡，但具体机制尚不清楚。本项目拟①通过检测ADORA1在胃癌细胞及组织中的表达，分析ADORA1与胃癌临床病理特征的关系。②通过表达干预、药物靶向阻断ADORA1，研究其对胃癌细胞生物学功能的影响，并在动物模型的体内实验中加以验证，了解ω-3PUFAs通过ADORA1对胃癌生长的作用。探究ω-3PUFAs调控ADORA1下游信号并启动凋亡程序的分子机制。阐明ω-3PUFAs通过ADORA1发挥抑癌作用的机制。为ω-3PUFAs应用于胃癌的辅助治疗提供理论依据。

胃癌患者大多存在不同程度的营养不良，严重影响了治疗效果及预后。安全、有效的辅助治疗能够改善患者预后及生活质量。ω-3多不饱和脂肪酸（ω-3PUFAs）作为一种特殊的营养素，其抗肿瘤的作用在许多研究中被发现。我们的前期研究发现ω-3PUFAs能够通过腺苷受体A 1（ADORA1）诱导胃癌细胞的凋亡，但具体机制尚不清楚。本项目通过检测ADORA1在胃癌细胞的表达，发现ADORA1的表达与细胞分化程度相关。在ADORA1低表达的胃癌细胞MKN45中经DHA、EPA作用后，发现ADORA1表达上调。而联合顺铂后ADORA1的表达明显增高。发现ω-3PUFAs协同顺铂通过调控ADORA1诱导胃癌细胞MKN45凋亡。为ω-3PUFAs在胃癌细胞中发挥的作用阐述了新的机制。也为ω-3PUFAs应用于胃癌的辅助治疗提供理论依据。