Miwa Takai, Miyu Takamoto, Yuka Amano, Mao Yamamoto, Koki Hara, Narumi Yashiro, Toshifumi Tsujiuchi
{"title":"诱导溶血磷脂酸（LPA）受体介导的信号传导调节用过氧化氢处理的癌症细胞的细胞运动和抗癌药物的存活。","authors":"Miwa Takai, Miyu Takamoto, Yuka Amano, Mao Yamamoto, Koki Hara, Narumi Yashiro, Toshifumi Tsujiuchi","doi":"10.1016/j.jbior.2023.100978","DOIUrl":null,"url":null,"abstract":"<div><p>Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is one of reactive oxygen species (ROS) and promotes malignant properties of cancer cells. Lysophosphatidic acid (LPA) signaling via LPA receptor (LPA<sub>1</sub> to LPA<sub>6</sub>) regulates a variety of cellular functions, such as cell growth, migration and differentiation. This study aimed to evaluate the effects of LPA receptors on the cell motility and survival to anticancer drugs by H<sub>2</sub>O<sub>2</sub> in colon cancer DLD-1 cells. To obtain H<sub>2</sub>O<sub>2</sub> treated (DLD- H<sub>2</sub>O<sub>2</sub>) cells, cells were maintained in culture medium containing H<sub>2</sub>O<sub>2</sub> (60 μM) for 2 months. <em>LPAR2</em> and <em>LPAR4</em> gene expressions were markedly elevated in DLD-H<sub>2</sub>O<sub>2</sub> cells. The cell motility of DLD-H<sub>2</sub>O<sub>2</sub> cells was significantly lower than that of DLD-1 cells. DLD-H<sub>2</sub>O<sub>2</sub> cell motility was suppressed by LPA<sub>2</sub> knockdown and stimulated by LPA<sub>4</sub> knockdown. The cell survival rates to fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP) of DLD-H<sub>2</sub>O<sub>2</sub> cells were significantly higher than those of DLD-1 cells. The cell survival rate to 5-FU of DLD-H<sub>2</sub>O<sub>2</sub> cells was decreased by LPA<sub>2</sub> knockdown. Conversely, LPA<sub>4</sub> knockdown enhanced the cell survival rate to 5-FU of DLD-H<sub>2</sub>O<sub>2</sub> cells. In the tumor microenvironment, high levels of H<sub>2</sub>O<sub>2</sub> production are observed under hypoxic conditions. The cell survival rate to 5-FU of DLD-H<sub>2</sub>O<sub>2</sub> cells cultured at 1% O<sub>2</sub> was significantly higher than that of DLD-1 cells cultured at 1% O<sub>2</sub>, correlating with <em>LPAR2</em> gene expression. The present results suggest that the induction of LPA receptor-mediated signaling plays an important role in regulating cellular functions of DLD-1 cells treated with H<sub>2</sub>O<sub>2</sub>.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Induction of lysophosphatidic acid (LPA) receptor-mediated signaling regulates cell motility and survival to anticancer drugs in cancer cells treated with hydrogen peroxide\",\"authors\":\"Miwa Takai, Miyu Takamoto, Yuka Amano, Mao Yamamoto, Koki Hara, Narumi Yashiro, Toshifumi Tsujiuchi\",\"doi\":\"10.1016/j.jbior.2023.100978\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is one of reactive oxygen species (ROS) and promotes malignant properties of cancer cells. Lysophosphatidic acid (LPA) signaling via LPA receptor (LPA<sub>1</sub> to LPA<sub>6</sub>) regulates a variety of cellular functions, such as cell growth, migration and differentiation. This study aimed to evaluate the effects of LPA receptors on the cell motility and survival to anticancer drugs by H<sub>2</sub>O<sub>2</sub> in colon cancer DLD-1 cells. To obtain H<sub>2</sub>O<sub>2</sub> treated (DLD- H<sub>2</sub>O<sub>2</sub>) cells, cells were maintained in culture medium containing H<sub>2</sub>O<sub>2</sub> (60 μM) for 2 months. <em>LPAR2</em> and <em>LPAR4</em> gene expressions were markedly elevated in DLD-H<sub>2</sub>O<sub>2</sub> cells. The cell motility of DLD-H<sub>2</sub>O<sub>2</sub> cells was significantly lower than that of DLD-1 cells. DLD-H<sub>2</sub>O<sub>2</sub> cell motility was suppressed by LPA<sub>2</sub> knockdown and stimulated by LPA<sub>4</sub> knockdown. The cell survival rates to fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP) of DLD-H<sub>2</sub>O<sub>2</sub> cells were significantly higher than those of DLD-1 cells. The cell survival rate to 5-FU of DLD-H<sub>2</sub>O<sub>2</sub> cells was decreased by LPA<sub>2</sub> knockdown. Conversely, LPA<sub>4</sub> knockdown enhanced the cell survival rate to 5-FU of DLD-H<sub>2</sub>O<sub>2</sub> cells. In the tumor microenvironment, high levels of H<sub>2</sub>O<sub>2</sub> production are observed under hypoxic conditions. The cell survival rate to 5-FU of DLD-H<sub>2</sub>O<sub>2</sub> cells cultured at 1% O<sub>2</sub> was significantly higher than that of DLD-1 cells cultured at 1% O<sub>2</sub>, correlating with <em>LPAR2</em> gene expression. The present results suggest that the induction of LPA receptor-mediated signaling plays an important role in regulating cellular functions of DLD-1 cells treated with H<sub>2</sub>O<sub>2</sub>.</p></div>\",\"PeriodicalId\":7214,\"journal\":{\"name\":\"Advances in biological regulation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in biological regulation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212492623000246\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in biological regulation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212492623000246","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Induction of lysophosphatidic acid (LPA) receptor-mediated signaling regulates cell motility and survival to anticancer drugs in cancer cells treated with hydrogen peroxide
Hydrogen peroxide (H2O2) is one of reactive oxygen species (ROS) and promotes malignant properties of cancer cells. Lysophosphatidic acid (LPA) signaling via LPA receptor (LPA1 to LPA6) regulates a variety of cellular functions, such as cell growth, migration and differentiation. This study aimed to evaluate the effects of LPA receptors on the cell motility and survival to anticancer drugs by H2O2 in colon cancer DLD-1 cells. To obtain H2O2 treated (DLD- H2O2) cells, cells were maintained in culture medium containing H2O2 (60 μM) for 2 months. LPAR2 and LPAR4 gene expressions were markedly elevated in DLD-H2O2 cells. The cell motility of DLD-H2O2 cells was significantly lower than that of DLD-1 cells. DLD-H2O2 cell motility was suppressed by LPA2 knockdown and stimulated by LPA4 knockdown. The cell survival rates to fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP) of DLD-H2O2 cells were significantly higher than those of DLD-1 cells. The cell survival rate to 5-FU of DLD-H2O2 cells was decreased by LPA2 knockdown. Conversely, LPA4 knockdown enhanced the cell survival rate to 5-FU of DLD-H2O2 cells. In the tumor microenvironment, high levels of H2O2 production are observed under hypoxic conditions. The cell survival rate to 5-FU of DLD-H2O2 cells cultured at 1% O2 was significantly higher than that of DLD-1 cells cultured at 1% O2, correlating with LPAR2 gene expression. The present results suggest that the induction of LPA receptor-mediated signaling plays an important role in regulating cellular functions of DLD-1 cells treated with H2O2.
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