Knockdown of TANK-Binding Kinase 1 Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular-Targeted Drugs

Frontiers in Pharmacology

Fang Sun¹  Xiaojuan Li¹  Huiwei Sun¹  Qiyu Jiang¹  Yantao Chai¹  Fengxia Du²  Shiwei Yang³  Haidong Tan³  Dongdong Han³ 

[1] Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Institute of Infectious Diseases, Beijing, China;Department of Pharmacy, Medical Support Center of PLA General Hospital, Beijing, China;Organ Transplant Center and Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing, China;

关键词: TANK-binding kinase 1;    advanced hepatocellular carcinoma;    molecular-targeted drugs;    epithelialmesenchymal transition;    drug resistance;    pro-survival;   

DOI  :  10.3389/fphar.2022.924523

来源: DOAJ

【 摘 要 】

The protein kinase, TANK-binding kinase 1 (TBK1), not only regulates various biological processes but also functions as an important regulator of human oncogenesis. However, the detailed function and molecular mechanisms of TBK1 in hepatocellular carcinoma (HCC), especially the resistance of HCC cells to molecular-targeted drugs, are almost unknown. In the present work, the role of TBK1 in regulating the sensitivity of HCC cells to molecular-targeted drugs was measured by multiple assays. The high expression of TBK1 was identified in HCC clinical specimens compared with paired non-tumor tissues. The high level of TBK1 in advanced HCC was associated with a poor prognosis in patients with advanced HCC who received the molecular-targeted drug, sorafenib, compared to patients with advanced HCC patients and a low level of TBK1. Overexpression of TBK1 in HCC cells induced their resistance to molecular-targeted drugs, whereas knockdown of TBK1 enhanced the cells’ sensitivity to molecular-targeted dugs. Regarding the mechanism, although overexpression of TBK1 enhanced expression levels of drug-resistance and pro-survival-/anti-apoptosis-related factors, knockdown of TBK1 repressed the expression of these factors in HCC cells. Therefore, TBK1 is a promising therapeutic target for HCC treatment and knockdown of TBK1 enhanced sensitivity of HCC cells to molecular-targeted drugs.

【 授权许可】

Unknown