Anti-inflammatory actions of plant-derived multiple monoclonal antibody CO17-1A?×?BR55 related with anti-cancer effects in AOM/DSS-induced colorectal cancer mouse via down-regulating of ERK1/2
곽동훈, 허성윤, 김창현, 김지수, 김선욱, 장규태, 주영국,
소속 상세정보
곽동훈 ( Kwak Dong-Hoon ) - Wonkwang University Institute of Glycosciences
허성윤 ( Heo Sung-Yun ) - Wonkwang University College of Natural Sciences Department of Biological Science
김창현 ( Kim Chang-Hyun ) - Dongguk University College of Medicine
김지수 ( Kim Ji-Su ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
김선욱 ( Kim Sun-Uk ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
장규태 ( Chang Kyu-Tae ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
주영국 ( Choo Young-Kug ) - Wonkwang University College of Natural Sciences Department of Biological Sciences
Abstract
Plant-derived multiple monoclonal antibody (mAb) CO17-1A?×?BR55 (mAbP CO17-1A?×?BR55) produced in transgenic tobacco plants were cross-pollinated with mAb CO17-1A and mAb BR55. Human anti-colorectal cancer multiple mAb CO17-1A?×?BR55 was cloned using pBI121 vector. Mice were given a single intraperitoneal injection of azoxymethane (AOM) with 10?mg/kg body weight. Starting 1 week after the injection, mice received 2% dextran sulfate sodium (DSS) in the drinking water for 1 week. In addition, the mice were injected intraperitoneal with mAbs dissolved in phosphate buffered saline (100?μg/mouse) twice per week for 4 weeks. Apoptotic cell death, expression of pro-apoptotic proteins, activity of inflammatory cytokines and ERK pathway phosphorylation were assayed by Western blot and TUNEL kit. mAbP CO17-1A?×?BR55 meaningfully and efficiently suppressed the development of AOM/DSS-induced colorectal inflammation and colorectal tumors, as determined by a reduced activation of inflammatory cytokines, number of colorectal tumor-induced mouse, number of tumor per mouse colon than other mAbs. Cell death by apoptosis was much increased in the mAbP CO17-1A?×?BR55-treated tumor compared with negative control. Apoptotic cell death and expression of pro-apoptotic proteins including Bax and cleaved caspase-3 were highest in treatment with mAbP CO17-1A?×?BR55. In addition, mAbP CO17-1A?×?BR55 was meaningfully decreased the expression of inflammatory cytokines, including COX-2, iNOS, p50 and p65, but the expression of PPARγ was significantly increased compared with AOM/DSS-induced carcinogenesis negative control. Moreover, mAbP CO17-1A?×?BR55 meaningfully repressed the ERK1/2 phosphorylation in AOM/DSS-induced colorectal tumors. Therefore, our results suggest that multiple mAbP CO17-1A?×?BR55 have meaningful effects of anti-inflammation related with the anti-carcinogenesis in AOM/DSS-induced colorectal tumor by inhibition of ERK1/2 phosphorylation.
키워드
Colorectal tumor; azoxymethane; mAbP CO17-1A x BR5, apoptosis; ERK1/2 phosphorylation; inflammation
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