Administration of VEGF receptor tyrosine kinase inhibitor increases VEGF production causing angiogenesis in human small-cell lung cancer xenografts

  • Authors:
    • Takaaki Sasaki
    • Sachie Tanno
    • Kiyoko Shibukawa
    • Shinobu Osanai
    • Junichi Kawabe
    • Yoshinobu Ohsaki
  • View Affiliations

  • Published online on: September 1, 2008     https://doi.org/10.3892/ijo_00000036
  • Pages: 525-532
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Abstract

Angiogenesis is mediated mainly by vascular endothelial growth factor (VEGF), and VEGF causes rapid growth in cancers, including human small-cell lung cancer (SCLC). The anti-angiogenic strategy of treating cancer using VEGF receptor (VEGFR) inhibition is currently of great interest. We tested the effects of the VEGFR2 tyrosine kinase inhibitor (TKI) vandetanib on the proliferation of two kinds of SCLC cell lines: SBC-1 cells, with detectable VEGFR2 expression and MS-1-L cells, without detectable VEGFR2 expression. To evaluate the anti-tumor and anti-angiogenic effects of vandetanib in vivo, we grafted SBC-1 and MS-1-L cells into mice. After a 3-week treatment, we measured the tumor size and histologically evaluated necrosis and apoptosis using H&E and TUNEL staining, respectively. The microvessels in the xenografts were also quantified by immunostaining of CD31. Vandetanib did not affect the proliferation of SBC-1 cells, but stimulated the growth of MS-1-L cells. In the SCLC xenograft model, vandetanib inhibited growth and tumor angiogenesis in a dose-dependent manner in SBC-1 xenografts. Vandetanib inhibited the growth of MS-1-L xenografts at a low dose (<12.5 mg/kg/day), but it did not affect tumor size or change microvessel counts at a higher dose. Interestingly, secretion of VEGF increased significantly in the MS-1-L cell line in the presence of a high dose of vandetanib in vitro. The effects of vandetanib on tumor angiogenesis were different in SBC-1 and MS-1-L cell lines. Production of angiogenic factors such as VEGF by the tumor potentially stimulates tumor angiogenesis and results in the acquisition of resistance to VEGFR TKI.

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September 2008
Volume 33 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sasaki T, Tanno S, Shibukawa K, Osanai S, Kawabe J and Ohsaki Y: Administration of VEGF receptor tyrosine kinase inhibitor increases VEGF production causing angiogenesis in human small-cell lung cancer xenografts. Int J Oncol 33: 525-532, 2008
APA
Sasaki, T., Tanno, S., Shibukawa, K., Osanai, S., Kawabe, J., & Ohsaki, Y. (2008). Administration of VEGF receptor tyrosine kinase inhibitor increases VEGF production causing angiogenesis in human small-cell lung cancer xenografts. International Journal of Oncology, 33, 525-532. https://doi.org/10.3892/ijo_00000036
MLA
Sasaki, T., Tanno, S., Shibukawa, K., Osanai, S., Kawabe, J., Ohsaki, Y."Administration of VEGF receptor tyrosine kinase inhibitor increases VEGF production causing angiogenesis in human small-cell lung cancer xenografts". International Journal of Oncology 33.3 (2008): 525-532.
Chicago
Sasaki, T., Tanno, S., Shibukawa, K., Osanai, S., Kawabe, J., Ohsaki, Y."Administration of VEGF receptor tyrosine kinase inhibitor increases VEGF production causing angiogenesis in human small-cell lung cancer xenografts". International Journal of Oncology 33, no. 3 (2008): 525-532. https://doi.org/10.3892/ijo_00000036