Fukui Rie, Kato Kohei, Okabe Kyoko, Kitayoshi Misaho, Tanabe Eriko, Fukushima Nobuyuki, Tsujiuchi Toshifumi
Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.
J Toxicol Pathol. 2012 Sep;25(3):225-8. doi: 10.1293/tox.25.225. Epub 2012 Oct 1.
Lysophosphatidic acid (LPA) acts as a simple phospholipid that interacts with G protein-coupled transmembrane LPA receptors. Recently, it has been reported that each LPA receptor plays different biological roles in acquisition of the malignant property of tumor cells. In this study, to assess the involvement of LPA receptor-3 (LPA(3)) in cell survival after treatment with anticancer drugs, we generated Lpar3-expressing FM3A-a3A9 cells from mouse mammary tumor FM3A cells and examined the cell survival rate after treatment with anticancer drugs compared with Lpar3-unexpressing cells. Cells were treated with 0.005 to 10 μM of cisplatin (CDDP) or doxorubicin (DOX) for 3 days. For the CDDP and DOX treatments, the cell survival rate of FM3A-a3A9 cells was significantly higher than that of Lpar3-unexpressing cells. The expression level of the Mdr1a gene in FM3A-a3A9 cells was higher than that of Lpar3-unexpressing cells, whereas no significant difference in multidrug resistance 1b (Mdr1b) and glutathione S-transferase mu1 (Gstm1) expressions was found. These results suggest that LPA(3) may enhance the cell survival rate after treatment with anticancer drugs in mouse mammary tumor cells, correlating with increased expression of the Mdr1 gene.
溶血磷脂酸（LPA）作为一种简单的磷脂，可与G蛋白偶联的跨膜LPA受体相互作用。最近有报道称，每种LPA受体在肿瘤细胞恶性特性的获得中发挥着不同的生物学作用。在本研究中，为了评估LPA受体3（LPA(3)）在抗癌药物治疗后细胞存活中的作用，我们从小鼠乳腺肿瘤FM3A细胞中生成了表达Lpar3的FM3A-a3A9细胞，并与未表达Lpar3的细胞相比，检测了抗癌药物治疗后的细胞存活率。细胞用0.005至10μM的顺铂（CDDP）或阿霉素（DOX）处理3天。对于CDDP和DOX处理，FM3A-a3A9细胞的细胞存活率显著高于未表达Lpar3的细胞。FM3A-a3A9细胞中Mdr1a基因的表达水平高于未表达Lpar3的细胞，而在多药耐药1b（Mdr1b）和谷胱甘肽S-转移酶mu1（Gstm1）表达方面未发现显著差异。这些结果表明，LPA(3)可能提高小鼠乳腺肿瘤细胞抗癌药物治疗后的细胞存活率，这与Mdr1基因表达增加相关。
