Kasuya Kazuhiko, Nagakawa Yuichi, Suzuki Minako, Tanaka Hiroaki, Ohta Hiroshi, Itoi Takao, Tsuchida Akihiko
Department of Digestive Surgery, Tokyo Medical University;
Exp Ther Med. 2011 Nov;2(6):1047-1052. doi: 10.3892/etm.2011.349. Epub 2011 Sep 5.
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.
目前，尚无针对胰腺神经内分泌癌（PNEC）的有效化疗方法。然而，抗血管生成疗法有望对PNEC这种高血管肿瘤有效。我们用抗血管内皮生长因子（VEGF）抗体贝伐单抗处理PNEC细胞系和低血管性胰腺导管细胞癌（DCC）细胞系，并比较这两种不同类型细胞系之间的抗肿瘤效果。使用了PNEC细胞系QGP-1以及DCC细胞系BxPC-3和AsPC-1。我们评估了这些细胞系在体外增殖和分泌VEGF的能力、贝伐单抗在体内给药的抗肿瘤效果以及在雨蛙素诱导的胰腺炎模型中贝伐单抗对胰腺的副作用。QGP-1和DCC细胞系的比较显示，在低氧环境下，QGP-1分泌的VEGF水平高于DCC细胞系，且贝伐单抗对QGP-1发挥了最显著的生长抑制作用；肿瘤内血管数量减少，增殖细胞百分比大致相同。在胰腺炎模型中，给予贝伐单抗对胰腺炎或相关的低氧环境没有不利影响。贝伐单抗不会影响胰腺本身；因此，仅可预期其对胰腺神经内分泌肿瘤生长具有强大的抑制作用。
