Abstract
Aflibercept and arsenic trioxide drugs apply a cytotoxic effect on some human cancer cell lines. However, no more study has followed the effects of both drugs, especially arsenic trioxide, on oral squamous cell carcinoma (OCC). We used three OCC lines as a model to show the effect of these drugs on the genetically complex disease and investigate its targeted therapy. In this study, three human OCC cell lines were used from different patients. We treated cell lines with both medications to detect the effect and relevant molecular basis. First, methyl thiazolyl tetrazolium (MTT) assay was performed to detect the cytotoxicity effect and cell growth. Second, flow cytometry, gene and protein expression were performed to evaluate the anti-angiogenic effect on OCC lines. Next apoptosis was analyzed by flow cytometry. Finally, clonogenesis capacity and cell migration were assessed by colony formation assay and wound healing, respectively. Aflibercept had no cytotoxic effect on the three OCC cell lines but decreased cell growth rate. Arsenic trioxide had a significant cytotoxic effect on three cell lines. Our results demonstrated that both drugs significantly decreased endoglin, VEGFA, and VEGFB expression. In addition, Migration and colony formation assays confirmed that these drugs have significant anti-proliferative and anti-migration effect on oral carcinoma cells. These results revealed that both medications might be a potential drug for the management of oral cancer patients.
Highlights
Oral squamous cell carcinoma (OCC) accounts for over 90% of the oral malignancies (Tandon et al, 2017, Markopoulos, 2012)
methyl thiazolyl tetrazolium (MTT) assay: To assess the possible cytotoxic effects of the two medications on cells, all three cell lines were exposed to 5-30 μM arsenic trioxide and 20-2500 μg aflibercept for 24, 48, and 72 h
The results revealed that aflibercept had no cytotoxic effect on the three OCC cell lines
Summary
Oral squamous cell carcinoma (OCC) accounts for over 90% of the oral malignancies (Tandon et al, 2017, Markopoulos, 2012). According to a Ferlay and et al study in 2015, ∼300 000 new cases of oral malignancies were diagnosed worldwide and the mortality rate was about 145,000 (Ferlay et al, 2015). Researchers are attempting to find new treatment strategies for OCC (Gong et al, 2017). Another approach in cancer therapy is to use anti-angiogenic medications such as bevacizumab, aflibercept, sunitinib, pazopanib, ranibizumab, and arsenic trioxide (Teleanu et al, 2020). Aflibercept has been effective on several tumors in vitro and ex vivo It exerts its anti-angiogenic effects by regression of tumor vessels and vascular remodeling, and inhibition of neovascularization (Auvray et al, 2019, Ganjibakhsh et al, 2018)
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