Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
Anticancer Drugs. 2021 Jan 1;32(1):53-60. doi: 10.1097/CAD.0000000000000971.
The aim of the study is to investigate the role of GPR120 on the biological behavior of esophageal cancer cells in the setting of radiation and explore the mechanism. GPR120 knockdown was fulfilled by siRNA-mediated effects in two esophageal cancer cell lines Eca109 and EC9706. Colony formation, survival fraction calculation, viable cell evaluation by cell counting kit-8 assay and cell apoptosis analysis by phycoerythrin annexin V and 7-amino-actinomycin (7-AAD) staining and the flow cytometry examination was evaluated in Eca109 and EC9706 under the treatment of different radiation dosage. The mechanisms were explored by the evaluation of the Akt pathway and apoptosis protein level. Significantly decreased GPR120 mRNA and protein after GPR120 siRNA treatment compared to control siRNA treatment. Significantly decreased colony formation was found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells at the radiation dosage of 2, 4, 6 and 8 Gy. Moreover, decreased survival fraction number with increased sensitive enhancing ratio was also found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells. Decreased cell viability and increased cell apoptosis in GPR120 siRNA-treated esophageal cancer cells. GPR120 siRNA decreased the Akt phosphorylation and anti-apoptotic Bcl-2 expression level, but increased pro-apoptotic Bim expression level in esophageal cancer cell lines. GPR120 regulated the biological behavior of the esophageal cancer cells via affecting Akt pathway and apoptosis molecules. Moreover, GPR120 siRNA combined radiation treatment could be a therapeutic choice for esophageal cancer.
本研究旨在探讨 GPR120 在放射治疗环境下对食管癌细胞生物学行为的作用，并探讨其机制。通过在两种食管癌细胞系 Eca109 和 EC9706 中用 siRNA 介导的作用敲低 GPR120。在不同辐射剂量下，通过细胞集落形成、存活分数计算、细胞计数试剂盒-8 测定活细胞评估和藻红蛋白 Annexin V 和 7-氨基放线菌素 D（7-AAD）染色及流式细胞术检测评估 Eca109 和 EC9706 中的作用。通过评价 Akt 通路和凋亡蛋白水平来探讨机制。与对照 siRNA 处理相比，GPR120 siRNA 处理后 GPR120 mRNA 和蛋白水平显著降低。与对照 siRNA 处理组相比，GPR120 siRNA 处理的 Eca109 和 EC9706 细胞在 2、4、6 和 8 Gy 的辐射剂量下集落形成明显减少。此外，还发现 GPR120 siRNA 处理的 Eca109 和 EC9706 细胞的存活分数减少，且敏感增强比增加。与对照 siRNA 处理组相比，GPR120 siRNA 处理的食管癌细胞的细胞活力降低，细胞凋亡增加。GPR120 siRNA 降低了 Akt 磷酸化和抗凋亡 Bcl-2 表达水平，但增加了促凋亡 Bim 表达水平在食管癌细胞系中。GPR120 通过影响 Akt 通路和凋亡分子调节食管癌细胞的生物学行为。此外，GPR120 siRNA 联合放射治疗可能是治疗食管癌的一种选择。
