BACKGROUND AND AIM: It was commonly accepted that chemotherapeutic cytotoxicity was the main cause for hepatic failure in hepatocellular carcinoma patients after repeated transarterial chemoembolization (TACE). However, the effect of embolization-induced hypoxia on liver cirrhosis has rarely been concerned. METHODS: Serum levels of alanine aminotransferase, aspartate aminotransferase, and albumin were used to detect liver injury. Hepatic artery ligation was performed in carbon tetrachloride-induced rat hepatic fibrosis model to mimic the effect of hepatic hypoxia on liver fibrosis after TACE. Sirius Red staining and immunohistochemical analysis of alpha-smooth muscle actin (α-SMA) were used to detect the activation of hepatic stellate cells. Moreover, the expression of hypoxia and fibrosis-related molecules were analyzed at protein and/or mRNA level. RESULTS: Patients showed a significant increase in alanine aminotransferase and aspartate aminotransferase (P = 0.006), accompanied by a decrease in albumin (P = 0.005) after repeated TACE. Hepatic artery ligation significantly promoted carbon tetrachloride-induced rat liver fibrosis progression as indicated by Sirius Red and α-SMA staining, as well as increased expression of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF). Conditioned media of hypoxia-treated L02 cells induced the expression of Collagen I and α-SMA in LX-2 cells, which was inhibited by HIF-1α small interfering RNA. Finally, HIF-1α inhibitor LW6 attenuated the hypoxia-induced fibrosis progression in vivo. CONCLUSION: Our data demonstrate that TACE-induced hepatic hypoxia aggravates the fibrosis progression in peritumoral liver tissue, thus leads to the deterioration of liver function. Intervention of HIF-1α might be a valuable strategy to optimize the efficacy and reduce the complication of TACE.
BACKGROUND AND AIM: It was commonly accepted that chemotherapeutic cytotoxicity was the main cause for hepatic failure in hepatocellular carcinomapatients after repeated transarterial chemoembolization (TACE). However, the effect of embolization-induced hypoxia on liver cirrhosis has rarely been concerned. METHODS: Serum levels of alanine aminotransferase, aspartate aminotransferase, and albumin were used to detect liver injury. Hepatic artery ligation was performed in carbon tetrachloride-induced rat hepatic fibrosis model to mimic the effect of hepatic hypoxia on liver fibrosis after TACE. Sirius Red staining and immunohistochemical analysis of alpha-smooth muscle actin (α-SMA) were used to detect the activation of hepatic stellate cells. Moreover, the expression of hypoxia and fibrosis-related molecules were analyzed at protein and/or mRNA level. RESULTS:Patients showed a significant increase in alanine aminotransferase and aspartate aminotransferase (P = 0.006), accompanied by a decrease in albumin (P = 0.005) after repeated TACE. Hepatic artery ligation significantly promoted carbon tetrachloride-induced ratliver fibrosis progression as indicated by Sirius Red and α-SMA staining, as well as increased expression of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF). Conditioned media of hypoxia-treated L02 cells induced the expression of Collagen I and α-SMA in LX-2 cells, which was inhibited by HIF-1α small interfering RNA. Finally, HIF-1α inhibitor LW6 attenuated the hypoxia-induced fibrosis progression in vivo. CONCLUSION: Our data demonstrate that TACE-induced hepatic hypoxia aggravates the fibrosis progression in peritumoral liver tissue, thus leads to the deterioration of liver function. Intervention of HIF-1α might be a valuable strategy to optimize the efficacy and reduce the complication of TACE.
Authors: Bernhard Scheiner; Gregor Ulbrich; Mattias Mandorfer; Thomas Reiberger; Christian Müller; Fredrik Waneck; Michael Trauner; Claus Kölblinger; Arnulf Ferlitsch; Wolfgang Sieghart; Markus Peck-Radosavljevic; Matthias Pinter Journal: United European Gastroenterol J Date: 2019-03-21 Impact factor: 4.623
Authors: Yun-Bing Wang; Rong Ma; Zhi-Biao Wang; Qiu-Ling Shi; Lian Zhang; Wen-Zhi Chen; Jian-Ping Gong; Jin Bai Journal: Front Oncol Date: 2022-03-28 Impact factor: 6.244
Authors: Constantine Frangakis; Jae Ho Sohn; Ahmet Bas; Julius Chapiro; Ruediger E Schernthaner; MingDe Lin; James P Hamilton; Timothy M Pawlik; Kelvin Hong; Rafael Duran Journal: Front Oncol Date: 2021-11-05 Impact factor: 6.244