angiotensin ii type 2 receptor signaling significantly attenuates growth of murine pancreatic carcinoma grafts in syngeneic mice血管紧张素ⅱ2型受体信号明显减弱小鼠胰腺移植癌的增长同基因的老鼠.pdf

Doi et al. BMC Cancer 2010, 10:67 /1471-2407/10/67 RESEARCH ARTICLE Open Access Angiotensin II type 2 receptor signaling significantly attenuates growth of murine pancreatic carcinoma grafts in syngeneic mice 1 2 1 1 1 Chiyo Doi , Noboru Egashira , Atsushi Kawabata , Dharmendra Kumar Maurya , Naomi Ohta , Deepthi Uppalapati1 1 1 1 1 , Rie Ayuzawa , Lara Pickel , Yuka Isayama , Deryl Troyer , 2 1* Susumu Takekoshi , Masaaki Tamura Abstract Background: Pancreatic cancer is one of the most aggressive human malignancies, with a very poor prognosis. To evaluate the effect of angiotensin II (Ang II) type 2 receptor (AT2) expression in the host’s body on the growth of pancreatic carcinoma, we have investigated the growth of mouse pancreatic ductal carcinoma grafts in syngeneic wild type and AT receptor-deficient (AT -KO) mice. 2 2 Methods: The role of AT2 receptor-signaling in stromal cells on the growth of murine pancreatic carcinoma cells (PAN02) was studied using various in vitro and in vivo assays. In vivo cell proliferation, apoptosis, and vasculature in tumors were monitored by Ki-67 immunostaining, TUNEL assay, and von Willebrand factor immunostaining, respectively. In the co-culture study, cell proliferation was measured by MTT cell viability assay. All the data were analyzed using t-test and data were treated as significant when p 0.05. Results: Our results show that the growth of subcutaneously transplanted syngeneic xenografts of PAN02 cells, mouse pancreatic ductal carcinoma cells derived from the C57/BL6 strain,