Attia Yasmin M, El-Abhar Hanan S, Al Marzabani Mahmoud M, Shouman Samia A
Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, Egypt, 11796.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, Egypt, 11562.
BMC Cancer. 2015 Nov 3;15:838. doi: 10.1186/s12885-015-1850-4.
Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate.
An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor.
Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well.
3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.
他莫昔芬是雌激素受体阳性（ER+）乳腺癌的标准内分泌治疗药物；然而，许多女性在长期治疗后仍会复发。3-溴丙酮酸是一种糖酵解抑制剂，已在体外和体内显示出高选择性抗肿瘤活性。本研究的目的是评估使用3-溴丙酮酸通过重新编程癌细胞代谢来增强他莫昔芬疗效的可能性。
使用不同技术对乳腺癌细胞系MCF7和T47D进行联合治疗的体外抗肿瘤活性以及凋亡、抗转移和抗血管生成潜力的筛选。此外，还对荷瘤小鼠进行了联合治疗的抗肿瘤作用研究。
我们的结果表明，单独使用任何一种药物均可调节细胞凋亡、血管生成和转移潜力；然而，它们的联合使用效果超过了单独使用。联合治疗方案增强了活化的半胱天冬酶-3、7和9，以及氧化应激，表现为丙二醛增加和谷胱甘肽水平降低。此外，联合治疗方案使用后，包括缺氧诱导因子-1α、血管内皮生长因子以及金属蛋白酶-2和9在内的血管生成和转移标志物均降低。体内研究进一步证实了这些结果，该研究表明肿瘤体积和血管生成减少，氧化应激增加。
在乳腺癌治疗中，3-溴丙酮酸与他莫昔芬联合使用时可能是一种有价值的化合物。
