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Biomed Pharmacother. 2014 Feb;68(1):65-9. doi: 10.1016/j.biopha.2013.10.010. Epub 2013 Nov 7.

Apoptotic activity and antitumor efficacy of PEGylated TNF-related apoptosis-inducing ligand (TRAIL) in a Mia Paca-2 cell-xenografted mouse model.

Author information

1
School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea.
2
Division of Biotechnology, The Catholic University of Korea, 43-1, Yeokgok 2-dong, Wonmi-gu, Bucheon-si, 420-743 Gyeonggi-do, Republic of Korea.
3
School of Pharmacy, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, 440-746 Suwon, Republic of Korea. Electronic address: ysyoun@skku.edu.

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.

KEYWORDS:

Antitumor efficacy; Apoptotic activity; Mia Paca-2; PEGylated TRAIL; Pancreatic cancer

PMID:
24268811
DOI:
10.1016/j.biopha.2013.10.010
[Indexed for MEDLINE]
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