Vascular endothelial growth factor (
VEGF) serves an important role in new blood vessel formation or angiogenesis, which is a critical event in
tumor growth and
metastasis.
Bevacizumab is a humanized
monoclonal antibody against
VEGF-A, whereas S-1 is a fluoropyrimidine
antineoplastic agent that induces apoptosis in various types of
cancer cells. The present study evaluated the antitumor effects of
bevacizumab in combination with
5-fluorouracil (5-FU) or S-1 against
oral squamous cell carcinoma (OSCC) in vitro and in vivo. Two human OSCC cell lines were used, namely the high
VEGF-A-expressing HSC-2 cells and the low
VEGF-A-expressing SAS cells. MTT assay was used to evaluate the effect of
bevacizumab and/or
5-FU against HSC-2 and SAS cell proliferation. Additionally, the antitumor effect of
bevacizumab was evaluated alone and in combination with S-1 against HSC-2
tumors in nude mice. S-1 (6.9 mg/kg/day) was administered orally every day for 3 weeks, and
bevacizumab (5 ml/kg/day) was injected intraperitoneally twice per week for 3 weeks. Apoptotic cells in mouse
tumors were detected using the TUNEL method, and cell proliferation and microvessel density (MVD) were determined by immunohistochemical staining of Ki-67 and CD31, respectively.
Bevacizumab alone did not inhibit OSCC cell proliferation in vitro, and did not exhibit any synergistic inhibitory effect in combination with
5-FU in vitro. However, combined
bevacizumab and S-1
therapy exerted synergistic and significant antitumor effects in vivo on HSC-2
tumor xenografts, and induced apoptosis in
tumor cells. Furthermore, this combination
therapy led to decreased MVD and cell proliferative abilities, as well as increased apoptosis in
residual tumors. The present findings suggested that the
bevacizumab plus
S-1 combination therapy may exert antitumor effects in high
VEGF-A-expressing OSCC cells.