Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer. However, its administration is associated with the dose-limiting adverse effect, peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is the major mechanism responsible for oxaliplatin-induced neuropathy. Some drug transporters have been identified as platinum complex transporters in kidney or tumor cells, but not yet in DRG. In the present study, we investigated oxaliplatin transporters and their contribution to peripheral neuropathy. We identified 12 platinum transporters expressed in DRG with real-time PCR, and their transiently overexpressing cells were established. After exposure to oxaliplatin, the accumulation of platinum in these overexpressing cells was evaluated using a coupled plasma mass spectrometer. Octn1/2- and Mate1-expressing cells showed the intracellular accumulation of oxaliplatin. In an animal study, peripheral neuropathy developed after the administration of oxaliplatin (4 mg/kg, intravenously, twice a week) to siRNA-injected rats (0.5 nmol, intrathecally, once a week) was demonstrated with the von Frey test. The knockdown of Octn1 in DRG ameliorated peripheral neuropathy, and decreased platinum accumulation in DRG, whereas the knockdown of Octn2 did not. Mate1 siRNA-injected rats developed more severe neuropathy than control rats. These results indicate that Octn1 and Mate1 are involved in platinum accumulation at DRG and oxaliplatin-induced peripheral neuropathy.
Pubmed ID: 30295925 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets ANXA3
View all literature mentionsThis monoclonal targets MATE1 (S-14)
View all literature mentionsThis polyclonal targets OCTN2
View all literature mentionsA software application for one-dimensional electrophoretic analysis of multi-labeled fluorophores. It was designed to analyze multi-channel fluorescence data from Fujifilm FLA-5000 and FLA-8000 scanning systems. The software also works with other scanners in the BAS/FLA series and with the LAS series.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Flp-In-293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsA software application for one-dimensional electrophoretic analysis of multi-labeled fluorophores. It was designed to analyze multi-channel fluorescence data from Fujifilm FLA-5000 and FLA-8000 scanning systems. The software also works with other scanners in the BAS/FLA series and with the LAS series.
View all literature mentionsThis monoclonal targets MATE1 (S-14)
View all literature mentionsThis polyclonal targets ANXA3
View all literature mentionsCell line Flp-In-293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets OCTN2
View all literature mentions