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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.

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In vitro and in vivo study: Ethanolic extract leaves of Azadirachta indica Juss. variant of Indonesia and Philippines suppresses tumor growth of hepatocellular carcinoma by inhibiting IL-6/STAT3 signaling