Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors. Here we studied the effects of the P2Y₂ receptor activation in different types of esophageal cancer. Esophageal tissue samples of healthy controls were used for P2Y₂R expression quantification. Two human esophageal cancer cell lines Kyse-450 (squamous cell carcinoma) and OE-33 (adenocarcinoma) were used to perform in vitro analysis of cell proliferation, migration, adhesion, and the signaling pathways involved in P2Y₂R activation. Data showed that P2Y₂R was expressed in biopsies of patients with ESCC and adenocarcinoma, as well as in the two human esophageal cancer cell lines studied. The RT-qPCR analysis demonstrated that OE-33 cells have higher P2RY2 expression than Kyse-450 squamous cell line. Results showed that P2Y₂R activation, induced by ATP or UTP, promoted esophageal cancer cells proliferation and colony formation. P2Y₂R blockage with the selective antagonist, AR-C 118925XX, led to decreased proliferation, colony formation and adhesion. Treatments with ATP or UTP activated ERK 1/2 pathway in ESCC and ECA cells. The P2Y₂R antagonism did not alter the migration of esophageal cancer cells. Interestingly, the esophageal cancer cell lines presented a distinct profile of nucleotide hydrolysis activity. The modulation of P2Y₂ receptors may be a promising target for esophageal cancer treatment.

食道癌是世界范围内的主要疾病，分为两种主要的亚型：食道鳞状细胞癌和食道腺癌。死亡率令人震惊，对食管癌发展所涉及的机制的了解变得至关重要。嘌呤能信号传导与许多疾病以及这些各种类型的肿瘤有关。在这里，我们研究了P2Y ₂受体激活在不同类型的食道癌中的作用。健康对照者的食道组织样本用于P2Y ₂R表达定量。两种人类食道癌细胞系Kyse-450（鳞状细胞癌）和OE-33（腺癌）用于进行细胞增殖，迁移，粘附以及涉及P2Y ₂ R激活的信号通路的体外分析。数据显示，P2Y ₂ R在ESCC和腺癌患者的活组织检查以及所研究的两种人类食道癌细胞系中均有表达。RT-qPCR分析表明，OE-33细胞比Kyse-450鳞状细胞株具有更高的P2RY2表达。结果表明，ATP或UTP诱导的P2Y ₂ R活化促进食管癌细胞增殖和集落形成。P2Y ₂用选择性拮抗剂AR-C 118925XX阻断R导致增殖，集落形成和粘附减少。ATP或UTP处理可激活ESCC和ECA细胞中的ERK 1/2途径。P2Y ₂ R拮抗作用不会改变食管癌细胞的迁移。有趣的是，食管癌细胞系表现出明显的核苷酸水解活性。P2Y ₂受体的调节可能是食管癌治疗的有希望的目标。