Sema3A drastically suppresses tumor growth in oral cancer Xenograft model of mice.

BMC Pharmacol Toxicol 2017 07 6;18(1):55. Epub 2017 Jul 6.

Department of Oral Surgery, Shengjing Hospital of China Medical University, Shenyang, 110001, China.

Background: Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment. Interestingly, the axonal sprouting inhibitor semaphorin 3A (Sema3A), a potent suppressor of tumor angiogenesis in various cancer models, is lowly expressed in human oral cancer. Thus, we hypothesized that overexpression of Sema3A in human oral cancer cells may have potential therapeutic effects.

Methods: The LentiSema3A-EGFP was first constructed and transduced to the tongue squamous cell carcinoma cell line SSC-9. Angiogenesis assay was performed with endothelial cell tube formation assay and chorioallantoic membrane (CAM) assay. Tumor xenografts model was used to evaluate the effect of Sema3a on the tumor growth. Finally, western blot was performed to study the mechanisms of inhibiting angiogenesis by Sema3A.

Results: In vitro and in vivo approaches revealed that Sema3A significantly inhibited tube formation of endothelial cells and reduced angiogenesis in CAM assay. In addition, overexpression of Sema3A in the tongue squamous cell carcinoma cell line SSC-9 resulted in significantly reduced angiogenesis and drastically suppressed tumor growth in mice. Mechanistically, Sema3A inhibited the phosphorylation of VEGFR2, as well as Src and FAK, downstream of the VEGF/VEGFR2 pathway.

Conclusion: Our results demonstrated that overexpression of Sema3A in oral cancer cells drastically suppressed tumor growth by inhibiting angiogenesis. Our findings provide a basis for the development of novel therapeutics in the management of oral cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40360-017-0163-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501443PMC
July 2017
50 Reads

Publication Analysis

Top Keywords

oral cancer
20
tumor growth
16
overexpression sema3a
12
tube formation
8
sema3a
8
drastically suppressed
8
cancer cells
8
suppressed tumor
8
cam assay
8
sema3a inhibited
8
reduced angiogenesis
8
human oral
8
tongue squamous
8
cell ssc-9
8
carcinoma cell
8
squamous cell
8
cell carcinoma
8
inhibiting angiogenesis
8
cancer
7
angiogenesis
6

References

(Supplied by CrossRef)

AA Forastiere et al.
J Natl Compr Cancer Netw 2005

J Casiglia et al.
Gen Dent 2001

KD Hunter et al.
Nat Rev Cancer 2005

J Folkman et al.
Semin Oncol 2002

P Baluk et al.
Curr Opin Genet Dev 2005

GL Semenza et al.
Cancer Metastasis Rev 2007

M Sabbah et al.
Drug Resist Updat 2008

S Pennacchietti et al.
Cancer Cell 2003

J Folkman et al.
Sci Am 1996

H Kikutani et al.
Nat Rev Immunol 2003

Similar Publications