Abstract

Abstract Organic cation transporters (OCTs) of the solute carrier family 22 have been identified as uptake transporters for the charge state of a substrate such as cationic drugs. The OCTs have an isoform of OCT1, OCT2, OCT3, and OCT6. Previously OCT1-3 have shown to related with intracellular uptake of anticancer platinum drugs such as cisplatin (CDDP) and oxaliplatin; however an association of OCT6 and platinum drugs is not well elucidated. We found decreased gene and protein expressions of OCT6 in CDDP resistant PC14/CDDP cells compared to those in parental lung adenocaricinoma PC14 cells. In contrast, the expression levels of OCT1-3 were not changed between PC14 and PC-14/CDDP cells. The intracellular concentration of CDDP also decreased in PC14/CDDP compared with the parental cell. To elucidate the OCT6 for uptake of CDDP, we established a forced expression of OCT6 cell line by a transfection an OCT6 vector to PC14/CDDP cells. We found that intracellular CDDP concentration are increased concomitant with decreased resistance to CDDP in OCT6 overexpressed PC14/CDDP cells. These results indicate that OCT6 is related with uptake of CDDP, and that the expression of OCT6 could be one of the resistant factors against CDDP in lung cancer cells. Citation Format: Daishi Kasai, Tetsuya Oguri, Takehiro Uemura, Hisatoshi Hijikata, Midori Yokoyama, Eiji Kunii, Osamu Takakuwa, Hirotsugu Ohkubo, Mikinori Miyazaki, Ken Maeno, Akio Niimi. OCT6 expression is associated with the resistance to cisplatin in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 886. doi:10.1158/1538-7445.AM2013-886

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