Background Oxaliplatin is a main chemotherapeutic agent in the treatment of advanced colorectal cancer. The response rate has been reported to be over 50%, especially when combined with a target agent. However, most patients develop resistance to oxaliplatin even in responding patients, leading to cancer related death due to organ dysfunction. Unfortunately the mechanism of resistance of oxaliplatin is unclear. In the present study, we tried to identify the role of Sphingosine Kinase 1 (SPHK1) involved in the acquired resistance to oxaliplatin using colon cancer cell line.

Method We treated HCT-116 colon cancer cell lines with gradient concentrations of oxaliplatin starting at the dose of IC50. After treated with initial dose of oxaliplatin for 48hrs, we collected the viable cell and then treated again with elevated dose of oxaliplatin. After prolonged period of exposure to low dose of oxaliplatin, we compared cell viable test and protein expression between HCT-116 wild cell and oxaliplatin treated HCT-116 cell line. We also investigated the change of response to oxaliplatin after tranfection of SPHK1 into wild type of HCT-116 cell line. The viability was determined by Neutral Red uptake assay.

Result After prolonged repeated exposure of low dose oxaliplatin, HCT-116 cell line showed resistance to oxaliplatin and expressed new protein. We identified this new protein as SPHK1 using protemics. Comparing the wild type and the resistance cell line, phosphorylated Akt, phosphorylated ERK, and PTEN expression were upregulated in the resistant cell line. After transfection of SPHK1 into the wild type HCT-116 cell line, response to oxaliplatin decreased comparing to the control group.

Conclusion Based on our data, SPH1K can be a potential factor for the acquired resistance to oxaliplatin in colon cancer. It is not known yet the association between SPHK1 and PTEN in the mechanism of resistance. Currently, we are conducting experiment to identify these associations and mechanism of acquired resistance using other cell lines and human tissue.

Citation Format: Hee Yeon Lee, Myung Ah Lee, Jin Hee Park. SPHK1 expression associated with acquired resistance to oxaliplatin in colon cancer cell lines. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C66.

©2015 American Association for Cancer Research.
2015