Anti-vascular endothelial growth factor antibody single therapy for pancreatic neuroendocrine carcinoma exhibits a marked tumor growth-inhibitory effect

Kasuya,Kazuhiko; Nagakawa,Yuichi; Suzuki,Minako; Tanaka,Hiroaki; Ohta,Hiroshi; Itoi,Takao; Tsuchida,Akihiko

doi:10.3892/etm.2011.349

Anti-vascular endothelial growth factor antibody single therapy for pancreatic neuroendocrine carcinoma exhibits a marked tumor growth-inhibitory effect

Authors:
- Kazuhiko Kasuya
- Yuichi Nagakawa
- Minako Suzuki
- Hiroaki Tanaka
- Hiroshi Ohta
- Takao Itoi
- Akihiko Tsuchida
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Affiliations: Department of Digestive Surgery, Tokyo Medical University Hospital, Shinjukuku, Tokyo 167-0023, Japan, Department of Clinical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan, Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan
Published online on: September 5, 2011 https://doi.org/10.3892/etm.2011.349
Pages: 1047-1052

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Abstract

At present, no effective chemotherapy for pancreatic neuroendocrine carcinoma (PNEC) exists. However, anti-angiogenic therapy is expected to be effective for PNEC, a hypervascular tumor. We treated PNEC and hypovascular pancreatic ductal cell carcinoma (DCC) cell lines with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and compared the antitumor effect between the two different types of cell lines. The PNEC cell line QGP-1 and the DCC cell lines BxPC-3 and AsPC-1 were used. We evaluated the ability of the cell lines to proliferate and secrete VEGF in vitro, the antitumor effect of bevacizumab administration in vivo and the side effects of bevacizumab on the pancreas in a caerulein-induced pancreatitis model. Comparison of the QGP-1 and DCC cell lines showed that QGP-1 secreted a higher level of VEGF under a hypoxic environment than the DCC cell line, and bevacizumab exerted the most marked growth-inhibitory effect on QGP-1; the number of intratumoral blood vessels decreased and the percentage of proliferating cells was approximately the same. In the pancreatitis model, bevacizumab administration did not adversely affect the pancreatitis or the associated hypoxic environment. Bevacizumab does not affect the pancreas itself; therefore, its potent inhibitory effect on the growth of pancreatic neuroendocrine tumors alone can be expected.

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