Abstract:
Background: Azadirachta indica Juss. has been shown to suppress cancer progression through a variety of mechanisms. In order to treat cancer progression, cancer immunotherapy is used to stimulate the immune system where immunosuppression is present in tumor microenvironments. Many cancer cells produce a lot of interleukin-6 (IL-6) and signal transducer activator of transcription 3 (STAT3). STAT3 plays a key role in suppressing the expression of critical immune activation regulators. IL-6-mediated STAT3 activation is common in the tumor microenvironment. Inhibiting the IL-6/STAT3 signaling pathway has become a therapeutic option for cancer progression. As vimentin is also expressed in hepatic stellate cells boosting cancer survival. We focused on the precise effect of extract from leaves of Azadirachta indica Juss, on inhibiting the IL-6/STAT3 signaling cascade on hepatocellular carcinoma by in vitro and in vivo study. Methods: In the in vitro study, the effect of Azadirachta indica Juss. variant Indonesia and Philippines against the expression of IL-6 and STAT3 was examined in liver cancer cell line. In the in vivo study, 24 male rats ( Rattus norvegicus) strain Wistar were induced by diethylnitrosamine and carbon tetrachloride (CCl 4). Based on the therapy given, the groups were divided into negative control, positive control, Indonesia extract, and Philippine extract. Expression of IL-6, STAT3, and vimentin were tested using immunohistochemistry staining. The data were analyzed using analysis of variance, which was then followed by the Tukey test. Results: Statistically significant difference in IL-6 and STAT3 was observed between the treatment groups and positive control group by in vitro study and in vivo study. Generally, there is no significant difference between treatment using Indonesian and Philippine leaves. Conclusion: Both therapy doses of Azadirachta indica variant in Indonesia and Philippines were able to reduce IL-6, STAT3 and vimentin expression of hepatocellular carcinoma cell by in vitro and in vivo experiment.
摘要:
背景:阿扎迪拉赫塔indicaJuss.已被证明通过多种机制抑制癌症进展。为了治疗癌症进展,癌症免疫疗法用于刺激肿瘤微环境中存在免疫抑制的免疫系统。许多癌细胞产生大量的白细胞介素-6(IL-6)和信号转导转录激活因子3(STAT3)。STAT3在抑制关键免疫激活调节因子的表达中起关键作用。IL-6介导的STAT3激活在肿瘤微环境中很常见。抑制IL-6/STAT3信号通路已经成为癌症进展的治疗选择。因为波形蛋白也在肝星状细胞中表达,从而促进癌症存活。我们专注于从印染朱斯的叶子中提取的精确效果,通过体外和体内研究抑制IL-6/STAT3信号级联对肝细胞癌的作用。方法:在体外研究中,AzadirachtaindicaJuss的效果.在肝癌细胞系中检测了印度尼西亚和菲律宾变体对IL-6和STAT3表达的影响。在体内研究中,用二乙基亚硝胺和四氯化碳(CCl4)诱导24只雄性大鼠(Rattusnorvegicus)品系Wistar。根据给予的治疗,分为阴性对照组,阳性对照,印度尼西亚提取物,和菲律宾提取物。使用免疫组织化学染色检测IL-6、STAT3和波形蛋白的表达。数据采用方差分析,然后是Tukey测试。结果:通过体外研究和体内研究,观察到治疗组与阳性对照组之间IL-6和STAT3的统计学差异。一般来说,使用印度尼西亚和菲律宾叶的处理之间没有显着差异。结论:通过体内外实验,印度尼西亚和菲律宾的两种治疗剂量的印字变种均能降低肝癌细胞IL-6,STAT3和波形蛋白的表达。