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Chlorogenic acid induces 4T1 breast cancer tumor's apoptosis via p53, Bax, Bcl‐2, and caspase‐3 signaling pathways in BALB/c mice
Journal of Biochemical and Molecular Toxicology ( IF 3.6 ) Pub Date : 2020-10-15 , DOI: 10.1002/jbt.22642
Zahra Changizi 1 , Azam Moslehi 2 , Ali Haeri Rohani 1 , Akram Eidi 1
Affiliation  

Despite all the new treatments, metastatic breast cancer (BC) causes many deaths. Chlorogenic acid (CGA) is a polyphenol compound with various pharmacological traits, such as anticancer properties. Targeting apoptotic death pathways has been propounded as the most effective therapeutic method in various cancers. In the current study, apoptotic agents such as p53, Bax, Bcl‐2, and caspase‐3 have been investigated. The experimental groups included saline, BC, CGA, protective (PR), and treatment (TM) groups. First, 4T1 mouse BC was established and then the effects of treatment with CGA were investigated through measurement of tumor weight and volume, metastatic nodules, liver biochemical tests, hematoxylin and eosin (H&E), immunohistochemistry (IHC) staining, and real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) in experimental groups. The findings showed that CGA reduced tumor weight and volume in the PR group (P < .05) and in the TM group (P < .001). Surprisingly, it eliminated the tumors in the TM group. Metastatic nodules in the PR and TM groups were significantly reduced as compared with the BC group (P < .001). The evaluation by H&E staining showed cell apoptosis in both the PR and TM groups. The results of real‐time RT‐PCR showed that CGA therapy increased the expression ratio of Bax/Bcl‐2 (P < .001 and P < .05, respectively) and the expression of p53 (P < .001 and P < .05, respectively) and caspase‐3 genes (P < .01) in the PR and TM groups. The IHC data regarding the Bax/Bcl‐2 ratio confirmed the other results (P < .001). The findings demonstrate that CGA plays a significant role in the induction of apoptosis and the treatment of 4T1 BC tumors in BALB/c mice.

中文翻译:

绿原酸通过p53,Bax,Bcl-2和caspase-3信号通路在BALB / c小鼠中诱导4T1乳腺癌肿瘤的凋亡

尽管有所有新疗法,转移性乳腺癌(BC)导致许多死亡。绿原酸(CGA)是一种具有多种药理特性(例如抗癌特性)的多酚化合物。已经提出靶向凋亡性死亡途径是各种癌症中最有效的治疗方法。在当前的研究中,已经研究了凋亡因子,例如p53,Bax,Bcl-2和caspase-3。实验组包括生理盐水,BC,CGA,保护组(PR)和治疗组(TM)。首先,建立4T1小鼠BC,然后通过测量肿瘤的重量和体积,转移性结节,肝脏生化测试,苏木精和曙红(H&E),免疫组化(IHC)染色来研究CGA的治疗效果,实验组中的实时逆转录聚合酶链反应(RT-PCR)。研究结果表明,CGA可降低PR组的肿瘤重量和体积(P  <.05)和TM组(P  <.001)。出人意料的是,它消除了TM组的肿瘤。与BC组相比,PR和TM组的转移性结节明显减少(P  <.001)。通过H&E染色的评估显示PR和TM组中的细胞凋亡。实时RT-PCR结果显示CGA治疗可提高Bax / Bcl-2的表达率(分别为P  <.001和P  <.05)和p53的表达(P  <.001和P  <。 PR组和TM组分别为05和caspase-3基因(P <.01)。有关Bax / Bcl-2比率的IHC数据证实了其他结果(P <.001)。这些发现表明,CGA在诱导BALB / c小鼠的细胞凋亡和治疗4T1 BC肿瘤中起着重要作用。
更新日期:2020-10-15
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