Yong-Fang Ding1,2, Zhen-Hui Wu3, Ying-Jie Wei1,2, Luan Shu1,2, Yun-Ru Peng4,5. 1. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China. 2. Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China. 3. Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China. 4. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China. pengyunru@126.com. 5. Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China. pengyunru@126.com.
Abstract
PURPOSE: Hepatocellular carcinoma (HCC) cases are closely associated with chronic inflammation and fibrosis which is known as hepatic inflammation-fibrosis-cancer (IFC) axis. The aim of this study is to elucidate the development characteristics of the rat HCC model based on IFC axis. METHODS: The diethylnitrosamine (DEN)-induced rat HCC, which presents a stepwise histopathological progression that is similar to human HCC, was used to analyze the features of the different stages (inflammation, fibrosis, cancer). Rats were injected DEN at a dose of 30 mg/kg body weight twice a week for 11 weeks and the animals were observed until week 20. Time series sera and organ samples from the DEN animal model were collected to evaluate the dynamic changes. RESULTS: It was found that serum biochemical indicators (AST, ALT, ALP, TP, T-BIL, IL-6, TNF-α) from DEN-treated group were higher than that from control group. Fibrosis-related index in serum and live tissue were increased, respectively, from week 4 after DEN treatment. The expression of TGF-β1 and α-SMA in DEN-treated group was higher than that in control group. JAK2/STAT3 signaling was significantly up-regulated in DEN-treated group compared to that in control group. The histological examination confirmed that the hepatocarcinogenesis model was successfully established, and 100% of the animals in the DEN-exposed group developed liver tumors at 20 weeks. According to the pathological changes, the model characterized resulted in three stages: the inflammation stage (week 2-6), the fibrosis stage (week 8-12), and the HCC stage (week 14-20). CONCLUSIONS: The results suggested that the HCC development was associated with IFC axis. The serial progression of hepatocarcinogenesis was according to the sequence of hepatic inflammation, fibrosis and then hepatic tumor.
PURPOSE:Hepatocellular carcinoma (HCC) cases are closely associated with chronic inflammation and fibrosis which is known as hepatic inflammation-fibrosis-cancer (IFC) axis. The aim of this study is to elucidate the development characteristics of the rat HCC model based on IFC axis. METHODS: The diethylnitrosamine (DEN)-induced rat HCC, which presents a stepwise histopathological progression that is similar to human HCC, was used to analyze the features of the different stages (inflammation, fibrosis, cancer). Rats were injected DEN at a dose of 30 mg/kg body weight twice a week for 11 weeks and the animals were observed until week 20. Time series sera and organ samples from the DEN animal model were collected to evaluate the dynamic changes. RESULTS: It was found that serum biochemical indicators (AST, ALT, ALP, TP, T-BIL, IL-6, TNF-α) from DEN-treated group were higher than that from control group. Fibrosis-related index in serum and live tissue were increased, respectively, from week 4 after DEN treatment. The expression of TGF-β1 and α-SMA in DEN-treated group was higher than that in control group. JAK2/STAT3 signaling was significantly up-regulated in DEN-treated group compared to that in control group. The histological examination confirmed that the hepatocarcinogenesis model was successfully established, and 100% of the animals in the DEN-exposed group developed liver tumors at 20 weeks. According to the pathological changes, the model characterized resulted in three stages: the inflammation stage (week 2-6), the fibrosis stage (week 8-12), and the HCC stage (week 14-20). CONCLUSIONS: The results suggested that the HCC development was associated with IFC axis. The serial progression of hepatocarcinogenesis was according to the sequence of hepatic inflammation, fibrosis and then hepatic tumor.
Authors: Jun Chen; Evan LaGue; Junjie Li; Chendong Yang; Edward P Hackett; Manuel Mendoza; Jeffry R Alger; Ralph J DeBerardinis; Ian R Corbin; Kelvin L Billingsley; Jae Mo Park Journal: Anal Sens Date: 2021-09-14
Authors: Iftekhar Hassan; Hossam Ebaid; Ibrahim M Alhazza; Jameel Al-Tamimi; Shazia Aman; Ahmad M Abdel-Mageed Journal: Can J Gastroenterol Hepatol Date: 2019-03-03
Authors: Dina F Mansour; Heba M I Abdallah; Bassant M M Ibrahim; Rehab R Hegazy; Reham S E Esmail; Lubna O Abdel-Salam Journal: Asian Pac J Cancer Prev Date: 2019-08-01
Authors: Iftekhar Hassan; Azmat Ali Khan; Shazia Aman; Wajhul Qamar; Hossam Ebaid; Jameel Al-Tamimi; Ibrahim M Alhazza; Ahmed M Rady Journal: Sci Rep Date: 2018-01-26 Impact factor: 4.379