Abstract
BackgroundMultiple 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.MethodsThe 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.ResultsIn 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.ConclusionOur 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.
Highlights
Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment
The results showed that lower semaphorin 3A (Sema3A) levels were obtained in Squamous cell carcinoma (SCC-9) cells compared with R40LN and R40P cell lines (Fig. 1a)
The results showed that Sema3A was efficiently expressed in oral cancer cells after lentiSema3A transfection (Fig. 2b)
Summary
Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment. Oral cancer is generally regarded as a malignant tumor occurring in the oral cavity. Angiogenesis is important in the growth, metastasis, and prognosis of malignant solid tumors [5]. Formed tumor blood vessels have unique structural characteristics: the wall is not complete, with no smooth muscle components; it is composed only of endothelial cells and the basal membrane [6]. These properties enable fast growth and promote distant tumor metastasis [7,8,9].
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