Takahashi Kaede, Fukushima Kaori, Otagaki Shiho, Ishimoto Kaichi, Minami Kanako, Fukushima Nobuyuki, Honoki Kanya, Tsujiuchi Toshifumi
a Division of Molecular Oncology , Kindai University , Higashiosaka, Osaka , Japan.
b Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering , Kindai University , Higashiosaka, Osaka , Japan.
J Recept Signal Transduct Res. 2018 Feb;38(1):71-75. doi: 10.1080/10799893.2018.1426608.
Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits a variety of cellular responses via the activation of G protein-coupled transmembrane LPA receptors (LPA receptor-1 (LPA) to LPA). The aim of our study was to investigate effects of LPA receptors on soft agar colony formation in colon cancer cells treated with anticancer drugs. DLD1 cells were treated with fluorouracil (5-FU) or cisplatin (CDDP) for at least six months (DLD-5FU and DLD-CDDP cells, respectively). LPAR1 gene expression was markedly elevated in DLD-5FU cells. In contrast, DLD-CDDP cells showed the high expression of LPAR6 gene. In colony formation assay, DLD-5FU cells formed markedly large-sized colonies, while no colony formation was observed in DLD1 and DLD-CDDP cells. The large-sized colonies formed in DLD-5FU cells were suppressed by LPA knockdown. In contrast, LPA knockdown increased the size of colonies. In addition, DLD-5FU cells were further treated with CDDP for three months (DLD-C-F cells). DLD-CDDP cells were also treated with 5-FU (DLD-F-C cells). DLD-C-F cells formed large-sized colonies, but not DLD-F-C cells, correlating with LPAR1 and LPAR6 gene expression levels. These results suggest that LPA and LPA may regulate the colony formation activity in DLD1 cells treated with anticancer drugs.
溶血磷脂酸（LPA）是一种简单的生理性脂质，通过激活G蛋白偶联的跨膜LPA受体（从LPA受体-1（LPA）到LPA）表现出多种细胞反应。我们研究的目的是调查LPA受体对用抗癌药物处理的结肠癌细胞在软琼脂中集落形成的影响。用氟尿嘧啶（5-FU）或顺铂（CDDP）处理DLD1细胞至少六个月（分别为DLD-5FU和DLD-CDDP细胞）。LPAR1基因表达在DLD-5FU细胞中显著升高。相反，DLD-CDDP细胞显示LPAR6基因的高表达。在集落形成试验中，DLD-5FU细胞形成明显大尺寸的集落，而在DLD1和DLD-CDDP细胞中未观察到集落形成。DLD-5FU细胞中形成的大尺寸集落被LPA敲低所抑制。相反，LPA敲低增加了集落的大小。此外，用CDDP进一步处理DLD-5FU细胞三个月（DLD-C-F细胞）。也用5-FU处理DLD-CDDP细胞（DLD-F-C细胞）。DLD-C-F细胞形成大尺寸集落，但DLD-F-C细胞未形成，这与LPAR1和LPAR6基因表达水平相关。这些结果表明，LPA和LPA可能调节用抗癌药物处理的DLD1细胞中的集落形成活性。
