Regulation of cellular responses to X-ray irradiation through the activation of lysophosphatidic acid (LPA) receptor-3 (LPA3) and LPA2 in osteosarcoma cells.
Pathol Res Pract
; 257: 155293, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38615508
ABSTRACT
Lysophosphatidic acid (LPA) binds to its specific G protein-coupled LPA receptors (LPA1 to LPA6), resulting in the activation of various cellular functions. LPA receptor-mediated signaling facilitates tumor progression in human malignancies. In the present study, we investigated whether LPA receptor-mediated signaling contributes to cellular responses to X-ray irradiation in osteosarcoma MG-63 cells. After X-ray irradiation (2, 4 and 8â¯Gy), LPAR2 and LPAR3 expression levels in MG-63 cells were significantly elevated in a dose-dependent manner, but no change of LPAR1 expression level was observed. The cell growth activities of MG-63 cells irradiated with X-rays (2, 4 and 8â¯Gy) were reduced by LPA. Conversely, LPA3 agonist (2â¯S)-OMPT enhanced the cell growth activities of X-ray irradiated MG-63 cells. The cell movement of MG-63 cells exposed to X-ray irradiation (8â¯Gy) was inhibited by (2â¯S)OMPT. In cell survival assay, (2â¯S)-OMPT suppressed the cell survival to cisplatin (CDDP) of MG-63 cells irradiated with X-rays (8â¯Gy). The cell survival to CDDP of X-ray irradiated cells was elevated by LPA3 knockdown. Moreover, we evaluated the effects of LPA2 on the cell survival to CDDP of MG-63 cells exposed to X-ray irradiation (8â¯Gy). The cell survival to CDDP of X-ray irradiated cells was increased by LPA2 agonist GRI-977143 and reduced by LPA2 knockdown. These results suggest that LPA receptor-signaling participates in the modulation of cellular functions induced by X-ray irradiation in osteosarcoma cells.
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MEDLINE
Assunto principal:
Neoplasias Ósseas
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Osteossarcoma
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Receptores de Ácidos Lisofosfatídicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article