Anatomy Department, Faculty Veterinary Medicine, Kafrelsheikh University, Post Box 33516, El-Geish Street, Kafrelsheikh, Egypt.
Chemistry Department, Biochemistry, Faculty of Science, Tanta University, Egypt.
Biomed Pharmacother. 2017 Aug;92:870-878. doi: 10.1016/j.biopha.2017.06.005. Epub 2017 Jun 6.
Methotrexate (MTX) is commonly used as a standard chemotherapy for many cancers, however its usage required high doses thereby leading to severe adverse effects. In a trial to find a suitable neoadjuvant therapy to decrease MTX dosage without lowering its chemotherapeutic efficacy, we investigated the antitumor effect of trehalose (TRE) on mice bearing Ehrlich ascites carcinoma (EAC) and checked whether TRE can enhance the antitumor potential of MTX. Treatment with TRE induced anti-tumor effects against EAC as reveled by a remarkable decrease in body weight, tumor volume, count of viable tumor cells, expression of the anti-apoptotic gene Bcl2 as well as by a significant increase in mean survival time, life span and expression of the apoptotic gene caspase-3. TRE also caused a significant decrease in autophagic activity of EAC cells as evident by reduction in the expression of the autophagic gene Beclin 1 (Bec1) and the fluorescence intensity of autophagosome marker. Additionally, TRE restored the altered hematological and biochemical parameters and improved the disrupted hepatic tissues of EAC-bearing mice. Interestingly, co-administration of TRE and MTX showed highest anti-tumor effect against EAC. These data indicate that TRE enhances the antitumor potential of MTX and could be used as neoadjuvant drug to increase the efficacy of the antitumor drug, MTX.
甲氨蝶呤（MTX）通常被用作许多癌症的标准化疗药物，但其使用需要高剂量，从而导致严重的不良反应。在一项寻找合适的新辅助治疗方法的试验中，我们研究了海藻糖（TRE）对荷 Ehrlich 腹水癌（EAC）小鼠的抗肿瘤作用，并检查 TRE 是否可以增强 MTX 的抗肿瘤潜力。TRE 治疗诱导了对 EAC 的抗肿瘤作用，表现为体重、肿瘤体积、存活肿瘤细胞计数显著减少，抗凋亡基因 Bcl2 的表达降低，平均生存时间、寿命和凋亡基因 caspase-3 的表达显著增加。TRE 还导致 EAC 细胞的自噬活性显著降低，这表现在自噬基因 Bec1 和自噬体标记的荧光强度的表达减少。此外，TRE 恢复了荷 EAC 小鼠改变的血液学和生化参数，并改善了受损的肝组织。有趣的是，TRE 和 MTX 联合给药对 EAC 表现出最高的抗肿瘤作用。这些数据表明，TRE 增强了 MTX 的抗肿瘤潜力，可作为新辅助药物增加抗肿瘤药物 MTX 的疗效。
