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Nimbolide inhibits tumor growth by restoring hepatic tight junction protein expression and reduced inflammation in an experimental hepatocarcinogenesis

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World Journal of Gastroenterology 2020年第45期26卷 7131-7152页

作者： Amit Kumar Ram Balasubramaniyan Vairappan BH Srinivas Liver Diseases Research Lab Department of BiochemistryJawaharlal Institute of Postgraduate Medical Education and Research(JIPMER)Dhanvantari NagarPuducherry 605006India Department of Pathology Jawaharlal Institute of Postgraduate Medical Education and Research(JIPMER)Dhanvantari NagarPuducherry 605006India

BACKGROUND Altered tight junction(TJ)proteins are correlated with carcinogenesis and tumor *** is a tetranotriterpenoid that has been shown to have antioxidant and anti-proliferative properties;however,its anticancer effects and molecular mechanism in hepatocellular carcinoma(HCC)remains *** To investigate the effect of nimbolide on TJ proteins,cell cycle progression,and hepatic inflammation in a mouse model of *** HCC was induced in male Swiss albino mice(CD-1 strain)by a single intraperitoneal injection of 100 mg/kg diethylnitrosamine(DEN)followed by 80 ppm N-nitrosomorpholine(NMOR)in drinking water for 28 *** 28 wk,nimbolide(6 mg/kg)was given orally for four consecutive weeks in DEN/NMOR induced HCC *** the end of the 32nd week,all the mice were sacrificed and blood and liver samples were collected for various *** examinations of hepatic nodules were *** histology and HCC tumor markers such as alpha-fetoprotein(AFP)and glypican-3 were *** of TJ proteins,cell proliferation,and cell cycle markers,inflammatory markers,and oxidative stress markers were *** silico analysis was performed to confirm the binding and modulatory effect of nimbolide on zonula occludens 1(ZO-1),nuclear factor of kappa light polypeptide gene enhancer in B-cells(NF-κB),and tumor necrosis factor alpha(TNF-α).RESULTS We found nimbolide treatment at a concentration of 6 mg/kg to HCC mice reduced hepatic tumor size by 52.08%and tumor volume(Pproteins such as ZO-1 and occludin expression(Passociated nucleic acid binding protein expression(P<0.001)in HCC mice *** treatment to HCC mice also inhibited cell proliferation and suppressed cell cycle progression

关键词： Hepatocellular carcinoma Nimbolide Tight junction Inflammation Oxidative stress zonula occludens 1 associated nucleic acid binding protein

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