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Arginine deiminase inhibits pancreatic cancer cell invasion by blocking PI3K-AKT signaling pathway
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- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 24
- DOI:
- 10.11569/wcjd.v24.i24.3570
- Key Word:
- 胰腺肿瘤;精氨琥珀酸合成酶;精氨酸剥夺;侵袭转移;PI3K信号;Pancreatic cancer;Argininosuccinate synthase;Arginine deprivation;Invasion and metastasis;PI3K signaling
Abstract： 目的 研究精氨酸脱亚胺酶(arginine deiminase,ADI)对胰腺癌细胞株迁移、侵袭能力的影响及可能的分子机制.方法 选取精氨琥珀酸合成酶表达缺陷和表达阳性的胰腺癌细胞株PANC-1和BxPC-3接受含ADI培养基或普通培养基培养干预.细胞划痕及Transwell试验检测细胞迁移和侵袭能力;实时定量PCR技术及Western blot检测侵袭相关基因mRNA和蛋白的改变.Western blot和Transwell试验检测ADI联合PI3K信号抑制剂LY29400对PAN C-l细胞侵袭行为及分子的影响.结果 ADI可抑制PANC-1细胞的迁移、侵袭(P＜0.05),下调PANC-I细胞尿激酶型纤溶酶原激活因子、基质蛋白金属酶(matrix metalloproteinases,MMP)-2、MMP-9,和上调金属蛋白酶类组织抑制剂-2和E-Cadherin的mRNA和/或蛋白表达水平(P＜0.05);而对BxPC-3细胞侵袭能力影响不明显.ADI可下调PANC-1细胞PI3K/AKT/核转录因子-κB(nuclear factor-kappa B,NF-κB)信号通路蛋白p-AKT、p-p65的表达水平,而LY294002则协同ADI的这种作用,并协同下调MMP-2水平;Transwell侵袭试验也显示LY294002可协同ADI抑制胰腺癌细胞的侵袭能力(P＜0.05).结论 ADI通过阻断PI3K-AKT信号通路调控侵袭相关基因表达抑制胰腺癌细胞侵袭.
- [1]马秀玲,蒋与刚.精氨酸和一氧化氮合成的关系及其在免疫调节中的作用[J].2002,(1).
- [2]Muerkoster S,Kruse ML,Gehrz A,etc.Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death.[J].2003,22(21).
- [3]Macus Tien, Kuo,Niramol, Savaraj,Lynn G, Feun.Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes.[J].2010,1.
- [4]Min-Cong, Wang,Min, Jiao,Tao, Wu,etc.Polycomb complex protein BMI-1 promotes invasion and metastasis of pancreatic cancer stem cells by activating PI3K/AKT signaling, an ex vivo, in vitro, and in vivo study.[J].2016.
- [5]Rouzbeh, Daylami,Diego J, Muilenburg,Subbulakshmi, Virudachalam,etc.Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer.[J].2014,33.
- [6]Kelly MP,Jungbluth AA,Wu BW,etc.Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking expression of argininosuccinate synthetase.[J].2012,106(2).
- [7]Jiangbo, Liu,Jiguang, Ma,Zheng, Wu,etc.Arginine deiminase augments the chemosensitivity of argininosuccinate synthetase-deficient pancreatic cancer cells to gemcitabine via inhibition of NF-κB signaling.[J].2014,14.
- [8]Mao,Z.,Meng,S.,Wu,L.,etc.Expression of argininosuccinate synthetase in patients with hepatocellular carcinoma[J].2013,28(2).
- [9]Cao, Lei,Chen, Xin,Xiao, Xue,etc.Resveratrol inhibits hyperglycemia-driven ROS-induced invasion and migration of pancreatic cancer cells via suppression of the ERK and p38 MAPK signaling pathways[J].2016,49(2).
- [10]Li-Jiuan Shen,Karin Beloussow,Wei-Chiang Shen.Modulation of arginine metabolic pathways as the potential anti-tumor mechanism of recombinant arginine deiminase[J].2006,231(1).
- [11]Adrian Barbul.Arginine: Biochemistry, Physiology, and Therapeutic Implications[J].1986,10(2).
- [12]Seo Young Kim,Ki Won Lee,Jong-Eun Kim,etc.Arginine deiminase originating from Lactococcus lactis ssp. lactis American Type Culture Collection (ATCC) 7962 induces G1-phase cell-cycle arrest and apoptosis in SNU-1 stomach adenocarcinoma cells.[J].2009,102(10).
- [13]Cheol-Yong, Yoon,Young-Jun, Shim,Eun-Ho, Kim,etc.Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.[J].2007,120.
- [14].Cells derived from normal or cancer breast tissue exhibit different growth properties when deprived of arginine[J].2012,29(4).
- [15]Hidalgo M.Pancreatic cancer.[J].2010,362(17).
- [16]Wangpaichitr M,Savaraj N,Spector S,etc.Arginine deprivation as a targeted therapy for cancer.[J].2008,14(11).
- [17]Bowles TL,Kim R,Galante J,etc.Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase.[J].2008,123(8).