Amaya Koji, Ohta Tetsuo, Kitagawa Hirohisa, Kayahara Masato, Takamura Hiroyuki, Fujimura Takashi, Nishimura Gen-Ichi, Shimizu Koichi, Miwa Koichi
Department of Gastroenterologic Surgery, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, Japan.
Int J Oncol. 2004 Oct;25(4):849-56.
Pancreatic ductal cancer has higher angiotensin II concentrations compared with normal pancreas or other solid tumors. This study examined angiotensin II type 1 (AT1) receptor expression and the role of angiotensin II in proliferation and survival of human pancreatic cancer cells. All three pancreatic cancer cell lines studied, from well to poorly-differentiated types, HPAF-II, AsPC-1, and Panc-1, showed strong expression of AT1 receptor. In contrast, HT-29 human colon cancer cells showed extremely weak expression. Angiotensin II stimulated the growth of pancreatic cancer cells through MAP kinase activation but had no significant effect on proliferation of HT-29 colon cancer cells. In addition, angiotensin II significantly prevented cisplatin (CDDP)-induced apoptosis through NF-kappaB activation and the subsequent production of anti-apoptotic molecules, including survivin and Bcl-XL, in pancreatic cancer cells. These findings suggest that angiotensin II plays a role in the growth and chemoresistance of AT1-positive pancreatic cancer cells through its action as a potent mitogen and anti-apoptotic molecule.
与正常胰腺或其他实体瘤相比，胰腺导管癌中的血管紧张素II浓度更高。本研究检测了血管紧张素II 1型（AT1）受体的表达以及血管紧张素II在人胰腺癌细胞增殖和存活中的作用。所研究的三种胰腺癌细胞系，从高分化到低分化类型，HPAF-II、AsPC-1和Panc-1，均显示出AT1受体的强表达。相比之下，HT-29人结肠癌细胞显示出极弱的表达。血管紧张素II通过激活MAP激酶刺激胰腺癌细胞的生长，但对HT-29结肠癌细胞的增殖没有显著影响。此外，血管紧张素II通过激活NF-κB以及随后在胰腺癌细胞中产生包括生存素和Bcl-XL在内的抗凋亡分子，显著阻止顺铂（CDDP）诱导的凋亡。这些发现表明，血管紧张素II作为一种有效的促有丝分裂原和抗凋亡分子，在AT1阳性胰腺癌细胞的生长和化疗耐药中发挥作用。
