title: Apoptotic activity and antitumor efficacy of PEGylated TNF-related apoptosis-inducing ligand (TRAIL) in a Mia Paca-2 cell-xenografted mouse model.
abstract: The purpose of this study was to demonstrate the apoptotic activity and antitumor effect of PEGylated tumor necrosis factor-related apoptosis-inducing ligand (PEG-TRAIL) in pancreatic carcinoma Mia Paca-2 cells and in Mia Paca-2 cell-xenografted mice. PEG-TRAIL was prepared using mPEG-aldehyde (Mw 5 kDa). The apoptosis induced by PEG-TRAIL in Mia Paca-2 cells and in the tumors of Mia Paca-2 cell-xenografted mice was quantified by FACS analysis and using a TUNEL assay. Mia Paca-2 cell-xenografted BALB/c nu/nu mice were administered intratumoral injections of PEG-TRAIL (50 μg/mouse/injection) every 3 days from day 0 (~4 weeks after xenografting) to day 15. Tumor volumes were measured every 3 days from day 0 to day 27. PEG-TRAIL displayed obvious apoptotic activity in Mia Paca-2 cells; the FACS signal was shifted to the apoptotic area and the cells exhibited green fluorescence indicating apoptosis in the TUNEL assay. Furthermore, PEG-TRAIL was found to suppress tumors in Mia Paca-2 cell-xenografted mice (tumor volumes: 183.9±134.1 for PEG-TRAIL vs. 1827.3±264.5 mm(3) for saline control). In addition, in vivo TUNEL assays of tumor tissues showed that the antitumor effect of PEG-TRAIL was due apoptosis. Our findings provide clear in vivo evidence of the antitumor potential of PEG-TRAIL in a Mia Paca-2 cell-xenografted mouse model based of pancreatic cancer.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Byeon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea.
authors.forename: Ji Su
authors.initials: JS
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Division of Biotechnology, The Catholic University of Korea, 43-1, Yeokgok 2-dong, Wonmi-gu, Bucheon-si, 420-743 Gyeonggi-do, Republic of Korea.
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea.
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea. Electronic address: ysyoun@skku.edu.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C552093:PEGylated tumor necrosis factor-related apoptosis-inducing ligand; D011993:Recombinant Fusion Proteins; D011092:Polyethylene Glycols
keywords: Antitumor efficacy; Apoptotic activity; Mia Paca-2; PEGylated TRAIL; Pancreatic cancer