scholarly journals Abstract 1996: Nuclear factor (erythroid-derived 2)-like 2 promotes tumor-initiating cell lineage and drug resistance in hepatocellular carcinoma

Author(s):  
Hoi Wing Leung ◽  
Terence Kin Wah Lee
2021 ◽  
Vol 499 ◽  
pp. 2
Author(s):  
Hoi Wing Leung ◽  
Eunice Yuen Ting Lau ◽  
Carmen Oi Ning Leung ◽  
Martina Mang Leng Lei ◽  
Etienne Ho Kit Mok ◽  
...  

2020 ◽  
Vol 476 ◽  
pp. 48-56 ◽  
Author(s):  
Hoi Wing Leung ◽  
Eunice Yuen Ting Lau ◽  
Carmen Oi Ning Leung ◽  
Martina Mang Leng Lei ◽  
Etienne Ho Kit Mok ◽  
...  

2021 ◽  
Author(s):  
Jia-ming Xie ◽  
Yi-qun Sui ◽  
Xin-yu Feng ◽  
Zhen-yu Feng ◽  
Wei Li ◽  
...  

Abstract Background: To study the role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in hepatocellular carcinoma (HCC) and drug resistance.Methods: HCC cells (HepG2 and SMMC7721) were used in this study. Fura 2-AM was used to assess cytosolic free Ca2+ concentrations ([Ca2+]i) within the two HCC cell lines. Nimodipine (NMDP), a Ca2+ antagonist, was used to reduce cytosolic [Ca2+]i level. Proliferation of HCC was measured using cell counting kit-8 (CCK-8). The roles of TIGAR and Ca2+ in drug resistance of HCC cells were assessed using epirubicin (Epi), 5-fluorouracil (5-FU), or cisplatinum (DDP).Results: Knockdown of TIGAR significantly suppressed cell viability, reduced [Ca2+]i, restrained protein expression of Ca2+-activated cysteine proteinases (Calpain1 and 2), as well as blocked the activation of nuclear factor kappa B (NF-κB) through an increase of cytoplasmic NF-κB and reduction of nuclear NF-κB. However, overexpression of TIGAR (oeTIGAR) resulted in the opposite. Evidence also shows that oeTIGAR suppressed the sensitivity of HCC to Epi, which was retarded by NMDP as an additional treatment. TIGAR interference could enhance the sensitivity of HCCs with high TIGAR expression to drugs.Conclusions: TIGAR promoted HCC progression and induced drug resistance, and the mechanism involved was [Ca2+]i-mediated activation of Calpain 1 and 2 and NF-κB signaling.


2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Shin Maeda

Hepatocellular carcinoma (HCC) is the third largest cause of cancer deaths worldwide. The role of molecular changes in HCC have been used to identify prognostic markers and chemopreventive or therapeutic targets. It seems that toll-like receptors (TLRs) as well as the nuclear factor (NF)-κB, and JNK pathways are critical regulators for the production of the cytokines associated with tumor promotion. The cross-talk between an inflammatory cell and a neoplastic cell, which is instigated by the activation of NF-κB and JNKs, is critical for tumor organization. JNKs also regulate cell proliferation and act as oncogenes, making them the main tumor-promoting protein kinases. TLRs play roles in cytokine and hepatomitogen expression mainly in myeloid cells and may promote liver tumorigenesis. A better understanding of these signaling pathways in the liver will help us understand the mechanism of hepatocarcinogenesis and provide a new therapeutic target for HCC.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.


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