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Virol Res J 2017 Volume 1 Issue 3
International Virology Conference
October 30-31, 2017 | Toronto, Canada
Coxsackievirus type B3 is a potent oncolytic virus against KRAS‑mutant non‑small‑cell lung cancer
H Deng
1
, T D Sliva
2
, H Liu
1
, Y Xue
1
, Y Mohamud
1
, J Zhang
1
, W Lockwood
2
and
H Luo
1
1
St. Paul’s Hospital, Canada
2
British Columbia Cancer Agency, Canada
Background:
Lung cancer is one of the most leading causes of
cancer‑related death worldwide. Over 85% of lung cancers are
non‑small‑cell lung cancer (NSCLC), for which the 5‑year survival
rate is extremely low (~15.9%). Most NSCLCs are caused by the
accumulation of genomic alterations, among which epidermal
growth factor receptor (EGFR) mutation and KRAS mutation
are two of the most predominant types. Although patients
with EGFR‑mutant NSCLCs have manifested a good response to
EGFR inhibitors, there is a paucity of effective treatments for the
KRAS‑mutant NSCLCs and new strategies are urgently needed.
Coxsackievirus type B3 (CV‑B3) is a non‑enveloped, human
pathogenic enterovirus that causes mild flu‑like symptoms
in adults. Due to its highly lytic nature, CV‑B3 has yielded an
increased efficacy of viral‑mediated oncolysis as compared to
other viruses, which makes it as a good candidate for cancer
treatment.
Methods:
Seven NSCLC cell lines (A549, H2030, H23, H1975,
PC‑9, H3255 and HCC4006) and three normal lung epithelial
cells (HPL1D, HAE and BEAS2B) were selected for this study.
Cells were infected with CV‑B3 (MOI 0.01) for 48 hrs. Cytopathic
effects caused by virus infection were observed by light
microscope, followed by crystal violet staining. MTS assay were
conducted to examine the resistance of normal lung epithelial
cells upon CVB3 infection. The supernatants were collected
to determine the virus titres by plaque assay. Coxsackievirus
and adenovirus receptor (CAR) expression was examined via
western blot.
Results:
Our studies found that CV‑B3 treatment led to a
significant reduction of cell survival in KRAS‑mutant NSCLCs
but not EGFR‑mutant NSCLCs nor normal lung epithelial cells.
MTS assay results demonstrated CV‑B3 infection didn’t lead to a
significant enhancement of cell death in normal lung epithelial
cells. Furthermore, we showed that virus titres within the
supernatants of KRAS‑mutant NSCLCs are significantly higher
than both EGFR‑mutant NSCLCs and normal lung epithelial
cells. Finally, we demonstrated that CAR expression levels were
significantly increased in KRAS‑mutant NSCLCs.
Conclusions:
Our study found that CV‑B3 is an effective and safe
oncolytic virus against KRAS‑mutant NSCLCs.
Speaker Biography
Haoyu Deng is a PhD student from St. Paul’s Hospital, Canada. His supervisor is Dr.
Honglin Luo and his former major was surgery. The medical science of UBC has
become one of its priority fields which are making great contributions to the medical
development. His current project is about the functional role of Gab1 in heart disease,
especially looking at the mechanisms involved in the role of Gab1 in molecular
signaling pathways when cardiomyocytes are infected by CVB3.
e:
eric.deng@hli.ubc.ca