Abstract 34: Monocarboxylate transporters as potential therapeutic targets in human ovarian cancer

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Abstract Introduction- Cancer cells have the ability to favour glycolysis for the production of lactate even in the presence of sufficient levels of oxygen. This is known as the ‘warburg effect’ or ‘aerobic glycolysis’. As a consequence of this glycolytic switch, there is an accumulation of lactate within cells. Therefore, cells must remove this excess lactate in order to prevent cell death via intracellular acidosis. In order to do this cells use Monocarboxylate Transporters (MCTs), which are responsible for the transport of lactate in and out of cells. MCT1 and MCT4 have been found to be over expressed in many types of human cancers, including ovarian cancer. Aims- The aim of this study was to assess how changing the expression levels of MCT1 and MCT4 effects the growth and response to therapy of four Human Ovarian cancer cell lines (Skov3, Caov3, OV90 and Ovcar3). Methods- Cell lines were stably transfected to either over express MCT1 (Skov3, Caov3, and OV90 cells), MCT4 (OV90 cells) or to contain doxycycline inducible silencing of MCT4 (Skov3, Caov3 and Ovcar3 cells). The effect of changing the expression levels of MCT1 and MCT4 on the function of these cell lines was assessed. Assays to look at changes in cell proliferation, lactate accumulation and release, and the cytotoxicity of Paclitaxel and Carboplatin were determined in both normoxia (21% O2) and hypoxia (0.1/1% O2). Results- Over expressing MCT1 in the three human ovarian cell lines had no effect on cell growth or lactate release in normoxia or hypoxia. Also when MCT1 was over expressed in Skov3 and Caov3 cells there were no changes in their sensitivity to Carboplatin or Paclitaxel. However, when MCT1 was over expressed in OV90 cells, they became slightly more resistant to Paclitaxel. Over expressing MCT4 in OV90 cells also had no effect on cell growth in normoxia, but significantly more lactate was released by these cells. Secondly, when these cells were grown in hypoxia they survived for a greater period of time than wild type cells. This correlated with a much higher amount of lactate being released by these cells. Finally, these cells were more resistant to Paclitaxel than both the MCT1 over expressing cell lines and their wild type counterparts. Conclusions- Changing the expression levels of MCT1 and MCT4 in Human Ovarian cancer cells have an effect on normal cell function. This suggests that MCTs could be potential therapeutic targets in ovarian cancer. Citation Format: Amy Boyers, Ian Stratford. Monocarboxylate transporters as potential therapeutic targets in human ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 34.