Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
Biochem Biophys Res Commun. 2019 Sep 17;517(2):359-363. doi: 10.1016/j.bbrc.2019.07.092. Epub 2019 Jul 27.
Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA to LPA) contributes to the promotion of malignant potency in cancer cells. The cell motile activity are stimulated through the induction of LPA in melanoma cells treated with anticancer drugs. The present study aimed to investigate whether LPA signaling via LPA regulates chemoresistance in melanoma A375 cells. Cells were treated with cisplatin (CDDP) or dacarbazine (DTIC) every 24 h for 2 days. CDDP and DTIC treatment increased LPAR5 expressions. The cell survival rates of A375 cells treated with CDDP and DTIC were significantly decreased by LPA. In addition, LPAR5 expression was markedly elevated in long-term CDDP treated (A375-CDDP) cells. LPA decreased the cell survival rate of A375-CDDP cells treated with CDDP. To evaluate the roles of LPA in chemoresistance during tumor progression, highly migratory (A375-R11) cells were established from A375 cells. LPAR5 expression level was significantly lower in A375-R11 cells than in A375 cells. The cell survival rates of A375-R11 cells treated with CDDP and DTIC were increased, compared with A375 cells. Moreover, we generated LPA knockdown cells from A375 cells. The cell survival rates of A375 cells treated with CDDP and DTIC were significantly elevated by LPA knockdown. These results suggest that LPA signaling via LPA is involved in the modulation of chemoresistance in melanoma A375 cells.
溶血磷脂酸（LPA）通过 LPA 受体（LPA 至 LPA）的信号转导有助于促进癌细胞的恶性潜能。在接受抗癌药物治疗的黑色素瘤细胞中，通过诱导 LPA 可刺激细胞迁移活性。本研究旨在探讨 LPA 通过 LPA 信号转导是否调节黑色素瘤 A375 细胞的化疗耐药性。细胞每 24 小时用顺铂（CDDP）或达卡巴嗪（DTIC）处理 2 天。CDDP 和 DTIC 处理增加了 LPAR5 的表达。LPA 降低了用 CDDP 和 DTIC 处理的 A375 细胞的细胞存活率。此外，长期用 CDDP 处理的 A375-CDDP 细胞中 LPAR5 表达明显升高。LPA 降低了用 CDDP 处理的 A375-CDDP 细胞的细胞存活率。为了评估 LPA 在肿瘤进展过程中化疗耐药性中的作用，从 A375 细胞中建立了高迁移性（A375-R11）细胞。A375-R11 细胞中的 LPAR5 表达水平明显低于 A375 细胞。与 A375 细胞相比，用 CDDP 和 DTIC 处理的 A375-R11 细胞的细胞存活率增加。此外，我们从 A375 细胞中生成了 LPA 敲低细胞。LPA 敲低显著增加了用 CDDP 和 DTIC 处理的 A375 细胞的细胞存活率。这些结果表明，LPA 通过 LPA 的信号转导参与了黑色素瘤 A375 细胞化疗耐药性的调节。
Zotero 插件