Kita Tsubasa, Kadochi Yui, Takahashi Kaede, Fukushima Kaori, Yamasaki Eri, Uemoto Taiki, Hirane Miku, Fukushima Nobuyuki, Honoki Kanya, Tsujiuchi Toshifumi
Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Exp Cell Res. 2016 Mar 15;342(2):193-9. doi: 10.1016/j.yexcr.2016.03.008. Epub 2016 Mar 8.
Free fatty acids (FFAs) are dietary nutrients which mediate a variety of biological effects through binding to G-protein-coupled FFA receptors (FFARs). G-protein-coupled receptor 120 (GPR120) and GPR40 are identified as FFARs for long- and medium-chain fatty acids. Here we investigated whether GPR120 and GPR40 are involved in the acquisition of malignant properties in lung cancer cells. Three lung cancer RLCNR, LL/2 and A549 cells used in this study expressed GPR120 and GPR40 genes. The cell motile activities of all cells were significantly suppressed by a GPR40 antagonist GW1100. In addition, GPR40 knockdown inhibited the cell motile activity of A549 cells. In gelatin zymography, matrix metalloproteinase-2 (MMP-2) activity in GPR40 knockdown was significantly lower than that in control cells. Next, to evaluate effects of GPR120 and GPR40 on cellular functions induced by anti-cancer drug, the long-term cisplatin (CDDP) treated (A549-CDDP) cells were generated. The expression levels of GPR120 and GPR40 were significantly decreased in A549-CDDP cells. While A549-CDDP cells showed the high cell motile activity, GW1100 suppressed the cell motile activity of A549-CDDP cells. These results demonstrate that GPR120 negatively and GPR40 positively regulate cellular functions during tumor progression in lung cancer cells.
游离脂肪酸（FFAs）是膳食营养素，通过与G蛋白偶联的游离脂肪酸受体（FFARs）结合介导多种生物学效应。G蛋白偶联受体120（GPR120）和GPR40被确定为长链和中链脂肪酸的FFARs。在此，我们研究了GPR120和GPR40是否参与肺癌细胞恶性特性的获得。本研究中使用的三种肺癌细胞系RLCNR、LL/2和A549细胞均表达GPR120和GPR40基因。GPR40拮抗剂GW1100显著抑制了所有细胞的细胞运动活性。此外，GPR40基因敲低抑制了A549细胞的细胞运动活性。在明胶酶谱分析中，GPR40基因敲低组的基质金属蛋白酶-2（MMP-2）活性显著低于对照细胞。接下来，为了评估GPR120和GPR40对抗癌药物诱导的细胞功能的影响，我们构建了长期顺铂（CDDP）处理的（A549-CDDP）细胞。A549-CDDP细胞中GPR120和GPR40的表达水平显著降低。虽然A549-CDDP细胞表现出较高的细胞运动活性，但GW1100抑制了A549-CDDP细胞的细胞运动活性。这些结果表明，在肺癌细胞肿瘤进展过程中，GPR120起负调节作用，GPR40起正调节作用。
