Oxamate potentiates taxol chemotherapeutic efficacy in experimentally-induced solid ehrlich carcinoma (SEC) in mice

Several human cancers including the breast display elevated expression of Lactate dehydrogenase-A (LDH-A), the enzyme that converts pyruvate to lactate and oxidizes NADH to NAD⁺. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate also plays roles in promoting tumor inflammation and as a signaling molecule that stimulates tumor angiogenesis. Because of its essential role in cancer metabolism, LDH-A has been considered as a potential target for combination cancer therapy. Therefore, the current study investigated the possible anti-tumor effect of LDH inhibitor (oxamate) in a murine model of breast cancer [Solid Ehrlich Carcinoma (SEC)], alone and in combination with Taxol chemotherapy. The potential underlying mechanisms were also investigated. The results indicated that oxamate induced significant anti-tumor activity against the SEC. Mechanistically, the combination treatment was more efficient than paclitaxel monotherapy in reducing ATP, MDA, TNF-α and Il-17 contents in SEC. Moreover, the apoptotic and anti-angiogenic effects of the combination treatment were triggered more efficiently as compared to paclitaxel monotherapy, Therefore, oxamate may represent a promising agent that enhance the antitumor activity of paclitaxel.