PBK/TOPK promotes chemoresistance to oxaliplatin in hepatocellular carcinoma cells by regulating PTEN.

Abstract

Oxaliplatin (OXA) resistance limits the efficiency of treatment for hepatocellular carcinoma (HCC). Studies have shown that the PDZ-binding kinase (PBK) plays important roles in tumors. However, the role of PBK in HCC is still a problem. In this study, we explored whether PBK is involved in the chemoresistance to OXA in HCC. Expressions of PBK in six HCC cell lines and one human hepatocytes line were determined by real-time quantitative PCR and western blot analysis. SNU-182 and HepG2 cells were chosen to induce OXA resistance. PBK was silenced or overexpressed in OXA-resistant and sensitive cell lines. Then, cell proliferation, migration, and invasion were measured by cholecystokinin-8 assay and Transwell assay, respectively. The Cancer Genome Atlas dataset showed that PBK is highly expressed in HCC and signifies poor prognosis to patient with HCC. Results showed that expression of PBK in HCC cells was significantly higher than that in THLE2 cells, and it was further increased in OXA-resistant HCC cells. Silencing of PBK promoted the sensitivity of drug-resistant HCC cells to OXA. Overexpression of PBK relieved the apoptosis induced by OXA and promoted the migration and invasion of OXA-sensitive HCC cells. Thus, this study revealed that high PBK expression is correlated with OXA resistance in HCC cells, which may provide a promising therapeutic target for treating HCC.

• Authors: Hongmin Cao, Mei Yang, Yufeng Yang, Jiayan Fang, Yejia Cui
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 53 Issue 5 Pg. 584-592 (Apr 15 2021) ISSN: 1745-7270 [Electronic] China
• PMID: 33772548 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Oxaliplatin
• Mitogen-Activated Protein Kinase Kinases
• PDZ-binding kinase
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Carcinoma, Hepatocellular (drug therapy, enzymology, genetics)
• Drug Resistance, Neoplasm (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, enzymology, genetics)
• Mitogen-Activated Protein Kinase Kinases (genetics, metabolism)
• Oxaliplatin (pharmacology)
• PTEN Phosphohydrolase (genetics, metabolism)