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Effect of methyl jasmonate and 3-bromopyruvate combination therapy on mice bearing the 4 T1 breast cancer cell line.
Journal of Bioenergetics and Biomembranes ( IF 3 ) Pub Date : 2020-01-20 , DOI: 10.1007/s10863-019-09811-w
Somayeh Yousefi 1 , Parisa Darvishi 2 , Zeynab Yousefi 3 , Ali Akbar Pourfathollah 1, 4
Affiliation  

Cancer cells apply the Warburg pathway to meet their increased metabolic demands caused by their rapid growth and proliferation and also creates an acidic environment to promote cancer cell invasion. 3-bromopyruvate (3-BrP) as an anti-cancer agent disrupts glycolytic pathway. Moreover, one of the mechanism of actions of Methyl Jasmonate (MJ) is interference in glycolysis. Hence, the aim of this study was to evaluate MJ and 3-BrP interaction. MTT assay was used to determine IC50 and synergistic concentrations. Combination index was applied to evaluate the drug- drug interaction. Human tumor xenograft breast cancer mice was used to evaluate drug efficacy in vivo. Tumor size was considered as a drug efficacy criterion. In addition to drug efficacy, probable side effects of these drugs including hepatotoxicity, renal failure, immunotoxicity, and losing weight were evaluated. Serum alanine aminotransferase and aspartate aminotransferase for hepatotoxicity, serum urea and creatinine level for the possibility of renal failure and changes in body weight were measured to evaluate drug toxicity. IL10 and TGFβ secretion in supernatant of isolated splenocytes from treated mice were assessed to check immunotoxicity. 3-BrP synergistically augmented the efficacy of MJ in the specific concentrations. This polytherapy was more effective than monotherapy of 3-BrP, MJ, and also surprisingly cyclophosphamide as a routine treatment for breast cancer in the tumor bearing mice. These results have been shown by decrease in tumor volume and increase of tumor growth inhibition percentage. This combination therapy didn't have any noticeable side effects on kidney, liver, and immune system and body weight.

中文翻译:

茉莉酸甲酯和3-溴丙酮酸联合疗法对带有4 T1乳腺癌细胞系的小鼠的影响。

癌细胞利用Warburg途径来满足因其快速生长和增殖而导致的新陈代谢需求增加,并且还创造了酸性环境来促进癌细胞的入侵。3-溴丙酮酸(3-BrP)作为抗癌剂会破坏糖酵解途径。此外,茉莉酸甲酯(MJ)的作用机制之一是干扰糖酵解。因此,本研究的目的是评估MJ和3-BrP的相互作用。使用MTT测定法测定IC 50和协同浓度。应用组合指数评估药物相互作用。人肿瘤异种移植乳腺癌小鼠用于评估体内药物效力。肿瘤大小被认为是药物疗效标准。除了药物功效外,这些药物的可能副作用包括肝毒性,肾衰竭,免疫毒性,和减肥。测量血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶的肝毒性,测定血清尿素和肌酐水平以测定肾衰竭的可能性和体重变化,以评估药物毒性。评估处理过的小鼠分离的脾细胞上清液中IL10和TGFβ的分泌,以检查免疫毒性。3-BrP在特定浓度下协同增强了MJ的功效。这种多药疗法比3-BrP,MJ单药疗法更有效,而且令人惊讶的是环磷酰胺作为荷瘤小鼠乳腺癌的常规疗法。这些结果已通过减少肿瘤体积和增加肿瘤生长抑制百分比来显示。这种联合疗法对肾脏,肝脏,
更新日期:2020-04-21
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