Recombinant porcine NK-lysin inhibits the invasion of hepatocellular carcinoma cells in vitro.

Abstract

The therapeutics having ability to target cancer cells specifically and exhibit nominal cytopathic effect on normal healthy cells are highly significant for cancer therapeutic applications. Recombinant porcine natural killer lysin (rpNK-lysin) has proven cationic anti-bacterial and anti-tumor peptide. Herein, we report its anti-invasion and anti-metastasis effects on hepatocellular carcinoma (HCC) cells in vitro. We first investigate the maximum non-toxic concentration (MNTC) of rpNK-lysin for the normal hepato cells (L-02). Using MNTC rpNK-lysin, we explore anti-proliferative, anti-adhesive, anti-invasive and anti-metastatic effect of rpNK-lysin on three different HCC cells lines (SMMC-7721, 97-H and HepG2) through MTT, wound-healing, adhesion and invasion assay along with mRNA and protein expression. The results reveal that rpNK-lysin has potential to specifically inhibit HCC cells growth in a dose and time-dependent manner with a little cytopathic effect on the L-02 cells, effectively reduce migration, adhesion and invasion ability of HCC cells. rpNK-lysin significantly reduce Fascin1 expression, which subsequently decrease β-catenin expression and metaloproteinases (MMP-2 and MMP9). This study suggest that MNTC rpNK-lysin has an anti-invasion and anti-metastasis effect on HCC cells in vitro through inhibition of Fascin 1 expression which regulates Wnt/β-catenin signaling pathway by inducing β-catenin degradation and subsequently results in suppression of MMP-2 and MMP9 expression.

• Authors: Ajab Khan, Kuohai Fan, Na Sun, Wei Yin, Yaogui Sun, Panpan Sun, Ali Raza Jahejo, Hongquan Li
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 140 Pg. 1249-1259 (Nov 01 2019) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 31465800 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• NK-lysin
• Neoplasm Proteins
• Proteolipids
• RNA, Messenger
• Recombinant Proteins

Topics

• Animals
• Carcinoma, Hepatocellular (drug therapy, genetics, pathology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Shape (drug effects)
• Down-Regulation (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (drug therapy, genetics, pathology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Proteins (genetics, metabolism)
• Proteolipids (pharmacology, therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (pharmacology, therapeutic use)
• Swine