IMR Press / FBL / Volume 24 / Issue 7 / DOI: 10.2741/4775

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Berberine enhances the radiosensitivity of hepatoma cells by Nrf2 pathway
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1 Department of oncoradiology, Rui’an People’s Hospital and The Third Affiliated Hospital of Wenzhou Medical University, rui’an, Zhejiang, 325200, P. R. China
*Correspondence: hongjin5947348@sina.com (Yucheng Lin)
Front. Biosci. (Landmark Ed) 2019, 24(7), 1190–1202; https://doi.org/10.2741/4775
Published: 1 June 2019
(This article belongs to the Special Issue Leader sequences of coronavirus are altered during infection)
Abstract

Radiation therapy is a major treatment in hepatocellular carcinoma (HCC). Yet, this treatment is ineffective in HCC due to lack of radiosensitivity. For this reason, we examined whether berberine (BBR) might modify the radioresistance of HCC cells. BBR enhances the radiation-induced oxidative stress and apoptosis in Huh7 and HepG2 cells while it protectes HHL-5 cells from radiation damage. To test the importance of Nrf2, a master transcription factor in oxidative damage, the effect of BBR is studied in irradiated Nrf2-deficient cells. BBR fails to induce the radiosensitivity in Nrf2-deficient cells suggesting that Nrf2 is required for the effect of BBR. BBR suppresses the expression of Nrf2 signaling-related proteins (Nrf2, HO-1 and NQO-1) in Huh7 and HepG2 cells, demonstrating that BBR strengthens radiosensitivity via suppressing Nrf2 signaling pathway in HCC cells. Furthermore, experiment using xenografts in nude mice indicated that BBR enhances the growth inhibitory effect of radiation in a Nrf2-dependent manner in vivo. In conclusion, these results suggest that BBR is a promising potential sensitizer for the radiotherapy of HCC.

Keywords
Berberine
Hepatocellular carcinoma
Radioresistance
Nuclear factor E2-related factor-2
Radiosensitivity
Figures
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