Effects of lysophosphatidic acid (LPA) signaling via LPA receptors on cellular functions associated with ATP reduction in osteosarcoma cells treated with ethidium bromide
Effects of lysophosphatidic acid (LPA) signaling via LPA receptors on cellular functions associated with ATP reduction in osteosarcoma cells treated with ethidium bromide
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DOI：
10.1007/s10863-022-09933-8
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发表时间：
2022-03-08
影响因子：
3
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
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作者：
Kurisu, Rio;Takamoto, Miyu;Tsujiuchi, Toshifumi
溶血磷脂酸（LPA）通过LPA受体（LPA（1）至LPA（6））的信号传导在癌细胞中表现出多种恶性性质。细胞内ATP耗竭导致坏死和凋亡的发展。本研究旨在评估LPA受体介导的信号传导对与ATP减少相关的癌细胞功能调节的影响。从骨肉瘤MG-63细胞建立长期溴化乙锭（EtBr）处理的（MG-63-EtBr）细胞。MG-63-EtBr细胞内ATP含量明显低于MG-63细胞。LPAR 2、LPAR 3、LPAR 4和LPAR 6基因在MG 63-EtBr细胞中表达升高。MG-63-EtBr细胞的运动和侵袭能力明显高于MG-63细胞。LPA（4）和LPA（6）基因敲减可增加MG-63细胞的运动活性。在细胞存活测定中，每24小时用顺铂（CDDP）处理细胞3天。MG-63-EtBr细胞对CDDP的存活率低于MG-63细胞。LPA（2）基因敲低降低了MG-63细胞对顺铂的存活率。（2S）-OMPT（LPA（3）激动剂）可抑制MG-63细胞在顺铂作用下的存活.此外，LPA（4）和LPA（6）敲低可增强MG-63细胞对CDDP的存活。这些结果表明，通过LPA受体的LPA信号转导参与了EtBr处理的MG-63细胞中与ATP减少相关的细胞功能的调节。
Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA(1) to LPA(6)) exhibits a variety of malignant properties in cancer cells. Intracellular ATP depletion leads to the development of necrosis and apoptosis. The present study aimed to evaluate the effects of LPA receptor-mediated signaling on the regulation of cancer cell functions associated with ATP reduction. Long-term ethidium bromide (EtBr) treated (MG63-EtBr) cells were established from osteosarcoma MG-63 cells. The intracellular ATP levels of MG63-EtBr cells were significantly lower than that of MG-63 cells. LPAR2, LPAR3, LPAR4 and LPAR6 gene expressions were elevated in MG63-EtBr cells. The cell motile and invasive activities of MG63-EtBr cells were markedly higher than those of MG-63 cells. The cell motile activity of MG-63 cells was increased by LPA(4) and LPA(6) knockdowns. In cell survival assay, cells were treated with cisplatin (CDDP) every 24 h for 3 days. The cell survival to CDDP of MG63-EtBr cells was lower than that of MG-63 cells. LPA(2) knockdown decreased the cell survival to CDDP of MG-63 cells. The cell survival to CDDP of MG-63 cells was inhibited by (2 S)-OMPT (LPA(3) agonist). Moreover, the cell survival to CDDP of MG-63 cells was enhanced by LPA(4) and LPA(6) knockdowns. These results indicate that LPA signaling via LPA receptors is involved in the regulation of cellular functions associated with ATP reduction in MG-63 cells treated with EtBr.