We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mannose-mediated inhibitory effects of PA- MSHA on invasion and metastasis of hepatocellular carcinoma via EGFR/Akt/IκBβ/ NF-κB pathway.
- Authors
Li, Tao; Dong, Zhao‐Ru; Guo, Zong‐Yi; Wang, Cheng‐Hao; Zhi, Xu‐Ting; Zhou, Jian‐Wei; Li, Deng‐Ke; Chen, Ze‐Ting; Chen, Zhi‐Qiang; Hu, San‐Yuan
- Abstract
Background & Aims Elevation of high-mannose glycans is a common feature of malignant cells and has been suggested to be the basis for alternative cancer therapy for several years. Here we want to investigate the antitumour effect of pseudomonas aeruginosa-mannosesensitive haemagglutinin ( PA- MSHA), a genetically engineered heat-inactivated PA strain with mannose-sensitive binding activity, on hepatocellular carcinoma ( HCC). Methods Tumourigenicity and metastatic potentials of HCC were studied after PA- MSHA treatment by utilizing the in vitro/ in vivo model of HCC. Expression of apoptosis-associated proteins and epithelial-mesenchymal transition ( EMT) related genes were evaluated, and possible signalling pathways involved were investigated. Results PA- MSHA induced significant cell proliferation inhibition and cell cycle arrest of HCC through decreasing the levels of cyclins D1, cyclins E, CDK2, CDK4, proliferating cell nuclear antigen ( PCNA), and increasing the level of p21 and p27. Moreover, PA- MSHA suppressed the invasion, migration and adhesion of HCC through inhibiting epithelial-mesenchymal transition ( EMT). PA- MSHA also inhibited EGFR/Akt/IκBβ/ NF-κB pathway and overexpression of NF-κB significantly abrogated PA- MSHA induced EMT inhibition. In addition, competitive inhibition of the mannose binding activity of PA- MSHA by D-mannose significantly blocked its effect on cell cycle arrest and EMT. PA- MSHA also abrogated lung metastasis of HCC and significantly inhibited tumour growth in the in vivo study. Conclusions Our study demonstrated the essential role of EGFR/Akt/IκBβ/ NF-κB pathway in the inhibitory effect of PA- MSHA on invasion and metastasis of HCC through suppressing EMT, and revealed an attractive prospect of PA- MSHA as a novel candidate agent in the treatment of HCC.
- Subjects
PSEUDOMONAS aeruginosa; MANNOSE; LIVER cancer; CANCER treatment; HEMAGGLUTININ; CELL proliferation
- Publication
Liver International, 2015, Vol 35, Issue 4, p1416
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.12644