A20 enhances the radiosensitivity of hepatocellular carcinoma cells to 60Co-γ ionizing radiation.

Rui Liu,Yunyi Yang,Dongli Zhao,Suxia Han,Jinlu Ma,Xiaozhi Zhang,Du Meng

doi:10.18632/oncotarget.21860

Abstract

The radioresistance of hepatocellular carcinoma (HCC) cells is a critical obstacle for effectively applying radiotherapy (RT) in HCC treatment. NF-κB, an important transcription factor, can influence critical cell fate decisions by promoting cell survival or anti-apoptosis in response to cell-stress, e.g. chemotherapies or ionizing radiation (IR). A20, also named as tumor necrosis factor α induced protein 3 (TNFAIP3), is a dominant negative regulator of NF-κB pathway and its functions in HCC are largely unknown. The present work aimed to reveal the role of A20 plays in affecting the radiosensitivity of HCC cells. Higher expression of A20 was detected in hepatic non-tumor cell line or clinical specimens compared with HCC cell lines or clinical specimens. A20 decreased the expression of proteins mediating cellular stress/injury response or epithelial-mesenchymal transition (EMT) process. Overexpression of A20 via adenovirus enhanced the effect of 60Co-γ ionizing radiation (IR) on HCC cells’ injury, e.g. G2/M arrest or DNA double strands break (DSB). Moreover, A20 also enhanced the in vitro or in vivo survival inhibiting of HCC cells induced by IR. These results reveal the roles of A20 in HCC radiosensitization and overexpression of A20 would be a novel strategy for HCC radiotherapy.

Highlights

Liver diseases are a heavily medical burden in Asian-pacific region, especially in China [1]
Considerable proportion of patients infect with HBV or are from HBV related chronic hepatitis would progress into hepatocellular carcinoma (HCC), an end-stage liver diseases (ESLD), even with efficient anti-viral treatment [1, 2]
Endogenous protein levels of A20 in HCC cells and non-tumor cells were showed in Figure 1A, 1B, lower level of A20 expression was detected in three HCC cell lines, HepG2, MHCC-97H and MHCC-97L, comparing to L-02 cells, a non-tumor liver cell line

Summary

Introduction

Liver diseases are a heavily medical burden in Asian-pacific region, especially in China [1]. Considerable proportion of patients infect with HBV or are from HBV related chronic hepatitis would progress into hepatocellular carcinoma (HCC), an end-stage liver diseases (ESLD), even with efficient anti-viral treatment [1, 2]. Most patients are suffering from advanced HCC at the initial diagnosis, and exhibit poor prognosis after chemotherapy, due to the multi-drug resistance (MDR) of HCC cells to chemotherapeutical agents [5, 6]. Oral multitarget kinase inhibitors, such as sorafenib, were showed to attenuate HCC progress or metastasis; the five-year survival rate of HCC patients is still low [7,8,9,10]. Radiotherapy is still a preferred treatment for advanced HCC and the novel radiotherapy strategies seem promising [12, 13].

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Discussion

Conclusion