PURPOSE: The purposes of this study were to determine whether organic cation transporters (OCTs) can mediate platinum uptake, and whether OCT down-regulation confers resistance against cisplatin (CDDP) in cancer cells. METHODS: Two lung cancer cell lines, PC-6 and PC-14, and their CDDP-resistant derivatives, PC-6/CDDP and PC-14/CDDP, were analyzed. OCT expression levels were assayed using quantitative RT-PCR and Western blotting. Additionally, the effect of OCT6 overexpression, induced by transfection of the OCT6 gene SLC22A16 using a forced expression vector, on cellular sensitivity to CDDP and on intracellular platinum accumulation was measured using PC-14/CDDP cells. RESULTS: Both gene and protein expression of OCT6 were decreased in both CDDP-resistant cell lines compared with their expression in their respective parental cells. Intracellular accumulation of platinum was decreased in PC-14/CDDP cells compared with the parental cells after CDDP treatment. Furthermore, OCT6 overexpression induced by transfection of the OCT6 gene (SLC22A16) forced expression vector-sensitized PC-14/CDDP cells to CDDP and oxaliplatin (L-OHP) concomitant with increased intracellular concentration of platinum. CONCLUSION: OCT6 is a mediator of platinum uptake in cancer cells, and down-regulation of OCT6 is possibly one of the mechanisms of resistance against cisplatin in lung cancer.
PURPOSE: The purposes of this study were to determine whether organic cation transporters (OCTs) can mediate platinum uptake, and whether OCT down-regulation confers resistance against cisplatin (CDDP) in cancer cells. METHODS: Two lung cancer cell lines, PC-6 and PC-14, and their CDDP-resistant derivatives, PC-6/CDDP and PC-14/CDDP, were analyzed. OCT expression levels were assayed using quantitative RT-PCR and Western blotting. Additionally, the effect of OCT6 overexpression, induced by transfection of the OCT6 gene SLC22A16 using a forced expression vector, on cellular sensitivity to CDDP and on intracellular platinum accumulation was measured using PC-14/CDDP cells. RESULTS: Both gene and protein expression of OCT6 were decreased in both CDDP-resistant cell lines compared with their expression in their respective parental cells. Intracellular accumulation of platinum was decreased in PC-14/CDDP cells compared with the parental cells after CDDP treatment. Furthermore, OCT6 overexpression induced by transfection of the OCT6 gene (SLC22A16) forced expression vector-sensitized PC-14/CDDP cells to CDDP and oxaliplatin (L-OHP) concomitant with increased intracellular concentration of platinum. CONCLUSION:OCT6 is a mediator of platinum uptake in cancer cells, and down-regulation of OCT6 is possibly one of the mechanisms of resistance against cisplatin in lung cancer.
Authors: Kevin M Huang; Muhammad Erfan Uddin; Duncan DiGiacomo; Maryam B Lustberg; Shuiying Hu; Alex Sparreboom Journal: Expert Opin Drug Metab Toxicol Date: 2020-04-26 Impact factor: 4.481
Authors: Khine Myint; Riya Biswas; Yan Li; Nancy Jong; Stephen Jamieson; Johnson Liu; Catherine Han; Christopher Squire; Fabrice Merien; Jun Lu; Takeo Nakanishi; Ikumi Tamai; Mark McKeage Journal: Sci Rep Date: 2019-02-19 Impact factor: 4.379