Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Biomed Pharmacother. 2017 Nov;95:1565-1573. doi: 10.1016/j.biopha.2017.09.090. Epub 2017 Oct 6.
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.
几种人类癌症，包括乳腺癌，表现出乳酸脱氢酶-A（LDH-A）的高表达，该酶将丙酮酸转化为乳酸，并将 NADH 氧化为 NAD。事实上，肿瘤中的乳酸水平与转移增加、肿瘤复发和预后不良有关。乳酸还在促进肿瘤炎症和作为刺激肿瘤血管生成的信号分子方面发挥作用。由于其在癌症代谢中的重要作用，LDH-A 已被认为是联合癌症治疗的潜在靶点。因此，本研究在乳腺癌 [实体 Ehrlich 癌（SEC）] 的小鼠模型中单独和联合紫杉醇化疗研究了 LDH 抑制剂（氧代氨酸）的可能抗肿瘤作用，并探讨了其潜在的作用机制。结果表明，氧代氨酸对 SEC 具有显著的抗肿瘤活性。从机制上讲，联合治疗在降低 SEC 中 ATP、MDA、TNF-α 和 Il-17 含量方面比紫杉醇单药治疗更有效。此外，与紫杉醇单药治疗相比，联合治疗更有效地触发了凋亡和抗血管生成作用。因此，氧代氨酸可能代表一种有前途的药物，可增强紫杉醇的抗肿瘤活性。
