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Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma

  • Authors:
    • Yasutaka Itashiki
    • Koji Harada
    • Takanori Takenawa
    • Tarannum Ferdous
    • Yoshiya Ueyama
    • Katsuaki Mishima
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Oral and Maxillofacial Surgery, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan
    Copyright: © Itashiki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 730
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    Published online on: August 11, 2021
       https://doi.org/10.3892/ol.2021.12991
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Abstract

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.
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Spandidos Publications style
Itashiki Y, Harada K, Takenawa T, Ferdous T, Ueyama Y and Mishima K: Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma. Oncol Lett 22: 730, 2021.
APA
Itashiki, Y., Harada, K., Takenawa, T., Ferdous, T., Ueyama, Y., & Mishima, K. (2021). Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma. Oncology Letters, 22, 730. https://doi.org/10.3892/ol.2021.12991
MLA
Itashiki, Y., Harada, K., Takenawa, T., Ferdous, T., Ueyama, Y., Mishima, K."Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma". Oncology Letters 22.4 (2021): 730.
Chicago
Itashiki, Y., Harada, K., Takenawa, T., Ferdous, T., Ueyama, Y., Mishima, K."Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma". Oncology Letters 22, no. 4 (2021): 730. https://doi.org/10.3892/ol.2021.12991
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Spandidos Publications style
Itashiki Y, Harada K, Takenawa T, Ferdous T, Ueyama Y and Mishima K: Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma. Oncol Lett 22: 730, 2021.
APA
Itashiki, Y., Harada, K., Takenawa, T., Ferdous, T., Ueyama, Y., & Mishima, K. (2021). Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma. Oncology Letters, 22, 730. https://doi.org/10.3892/ol.2021.12991
MLA
Itashiki, Y., Harada, K., Takenawa, T., Ferdous, T., Ueyama, Y., Mishima, K."Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma". Oncology Letters 22.4 (2021): 730.
Chicago
Itashiki, Y., Harada, K., Takenawa, T., Ferdous, T., Ueyama, Y., Mishima, K."Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma". Oncology Letters 22, no. 4 (2021): 730. https://doi.org/10.3892/ol.2021.12991
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