A TGFβ Signaling Inhibitor, SB431542, Inhibits Reovirus-mediated Lysis of Human Hepatocellular Carcinoma Cells in a TGFβ-independent Manner.

Abstract

BACKGROUND/AIM:

Oncolytic reovirus, which is a non-enveloped virus possessing a 10-segmented double-stranded RNA genome, has been anticipated as a novel class of antitumor agent. Hepatocellular carcinoma (HCC) is considered to be a target suitable for reovirus-mediated virotherapy. Transforming growth factor (TGF)-β plays an important role in the pathogenesis of HCC. TGF-β-signaling inhibitors have proceeded to clinical trials as potential antitumor agents for HCC. On the other hand, TGF-β is involved in induction of expression of cathepsins B and L, which are important for reovirus infection. It remains to be examined whether TGF-β signaling inhibitors affect reovirus-mediated lysis of HCC cells. The aim of this study was to evaluate the effects of TGF-β-signaling inhibitors on tumor cell lysis efficiency of reovirus in human HCC cells.

MATERIALS AND METHODS:

Reovirus was added to four types of human HCC cell lines pretreated with one of three TGF-β type I receptor inhibitors: SB431542, A-83-01, or galunisertib (LY2157299). Cell viability, virus genome copy numbers, and virus protein expression were evaluated following reovirus infection.

RESULTS:

SB431542 significantly inhibited reovirus-mediated killing of human HCC cell lines, while A-83-01 and galunisertib did not inhibit.

CONCLUSION:

These data indicate that SB431542 inhibited reovirus-mediated lysis of human HCC cells in a TGF-β signaling-independent manner.

• Authors: Ikuho Ishigami, Naomi Shuwari, Tadataka Kaminade, Hiroyuki Mizuguchi, Fuminori Sakurai
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 5 Pg. 2431-2440 (May 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33952468 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
• Benzamides
• Dioxoles
• Epoxy Compounds
• Pyrazoles
• Quinolines
• RNA, Double-Stranded
• TGFB1 protein, human
• Transforming Growth Factor beta1
• cathestatin B
• Tyrosine
• LY-2157299

Topics

• Benzamides (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, genetics, pathology, virology)
• Cell Survival (drug effects)
• Dioxoles (pharmacology)
• Epoxy Compounds
• Humans
• Liver Neoplasms (drug therapy, genetics, pathology, virology)
• Orthoreovirus, Mammalian (drug effects, genetics)
• Pyrazoles (pharmacology)
• Quinolines (pharmacology)
• RNA, Double-Stranded (genetics)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (antagonists & inhibitors, genetics)
• Tyrosine (analogs & derivatives, genetics)