Osong Public Health Res Perspect.  2019 Aug;10(4):246-252. 10.24171/j.phrp.2019.10.4.08.

Cell Death Mechanisms in Esophageal Squamous Cell Carcinoma Induced by Vesicular Stomatitis Virus Matrix Protein

• Douzandegan Y
• Tahamtan A
• Gray Z
• Nikoo HR
• Tabarraei
• Moradi A

• KMID: 2456577
• DOI: http://doi.org/10.24171/j.phrp.2019.10.4.08

Abstract

OBJECTIVES
Vesicular stomatitis virus (VSV) is under development as an oncolytic virus due to its preferential replication in cancer cells and oncolytic activity, however the viral components responsible have not yet been determined. In this study the effects of VSV wild-type (wt) and M51R-mutant matrix proteins (M51R-mMP) on apoptosis, pyroptosis, necroptosis, and autophagy pathways, in an esophagus cancer cell line (KYSE-30) were investigated.
METHODS
The KYSE-30 cells were transfected with pcDNA3.1 plasmids encoding wt or M51R-mMP, and apoptosis, pyroptosis, necroptosis, and autophagy were evaluated 48 and 72 hours after transfection.
RESULTS
KYSE-30 cells transfected with VSV wt and M51R-mMPs significantly reduced cell viability to < 50% at 72 hours post-transfection. M51R-MP significantly increased the concentration of caspase-8 and caspase-9 at 48 and 72 hours post-transfection, respectively ( p < 0.05). In contrast, no significant changes were detected following transfection with the VSV wt plasmid. Moreover, VSV wt and M51R-mMP transfected cells did not change the expression of caspase-3. VSV wt and M51R-mMPs did not mMP change caspase-1 expression (a marker of pyroptosis) at 48 and 72 hours post-transfection. However, M51R-mMP and VSV wt transfected cells significantly increased RIP-1 (a marker of necroptosis) expression at 72 hours post-infection ( p < 0.05). Beclin-1, a biomarker of autophagy, was also induced by transfection with VSV wt or M51R-mMPs at 48 hours post-transfection.
CONCLUSION
The results in this study indicated that VSV exerts oncolytic activity in KYSE-30 tumor cells through different cell death pathways, suggesting that M51R-mMP may potentially be used to enhance oncolysis.

Keyword

apoptosis; autophagy; oncolytic viruses; plasmids; pyroptosis

MeSH Terms

Apoptosis
Autophagy
Carcinoma, Squamous Cell*
Caspase 3
Caspase 8
Caspase 9
Cell Death*
Cell Line
Cell Survival
Epithelial Cells*
Esophageal Neoplasms
Oncolytic Viruses
Plasmids
Pyroptosis
Transfection
Vesicular Stomatitis*
Viral Structures
Caspase 3
Caspase 8
Caspase 9