|
- 2018
沉默PPARγ对骨肉瘤MG-63细胞增殖的影响及相关机制
|
Abstract:
摘要 目的:探讨过氧化物酶体增殖物激活受体γ(PPARγ)基因沉默对骨肉瘤MG-63细胞增殖的影响及其机制.方法:将PPARγ shRNA(干扰质粒),scramble shRNA(阴性对照质粒)转染入骨肉瘤MG-63细胞中,Western blot检测PPARγ shRNA对PPARγ蛋白的抑制作用; MTT法观察PPARγ沉默对骨肉瘤MG-63细胞增殖的影响,克隆形成实验与检测PPARγ沉默对骨肉瘤MG-63细胞克隆形成能力的影响; Western Blot检测PPARγ沉默后对骨肉瘤MG-63细胞中细胞增殖相关蛋白p-AKT、p-GSK-3β、CyclinD1的蛋白表达水平的影响.结果: PPARγ在骨肉瘤MG-63 细胞中沉默成功; MTT及克隆形成实验结果显示沉默PPARγ可促进骨肉瘤MG-63细胞的增殖; Western Blot检测结果显示PPARγ沉默上调骨肉瘤MG-63细胞p-AKT、p-GSK-3β、CyclinD1蛋白的表达.结论:沉默PPARγ可能通过调控Akt/GSK-3β/ CyclinD1信号通路促进骨肉瘤MG-63细胞的增殖.
[1] | YUUTA K, KOJI Y, AKIHIKO N, et al.Chondroblastic osteosarcoma arising from the pleura:report of acase[J].Surg Today, 2009, 39(12):1064-1067. |
[2] | CARRLE D, BIELACK S.Osteosarcoma lung metastases detection and principles of multimodal therapy[J].Cancer Treat Res, 2009, 152: 165-184. |
[3] | XU F,REN Y,GONG C, et al.Effect of PPARγ agonist on OPG/RANKL secreted by MG-63 cells[J]. Orthopaedics,2014,5(1):4-5. |
[4] | 关红亚,张海风,宋石,等.大豆苷元激活过氧化物酶体增殖子激活受体γ通路抑制人骨肉瘤MG63细胞的侵袭和迁移[J].中华实验外科杂志,2015,32(7):1563-1565. |
[5] | GUAN H Y, ZHANG H F,SONG S, et al.Daidzein suppresses invasion and metastasis of human osteosarcoma MG63 cells through activating peroxisome proliferator-activated receptor γ signal pathway[J]. Chinese Journal of Experimental Surgery,2015,32(7):1563-1565. |
[6] | MALUMBRES M, BARBACID M.Cell cycle, CDKs and cancer: a changing paradigm[J]. Nat Rev Cancer, 2009, 9(3): 153-166. |
[7] | TAN X L, ZHANG Y H,CAI J P, et al.5-(Hydroxymethyl)-2-furaldehyde inhibits adipogenic and enhances osteogenic differentiation of rat bone mesenchymal stem cells[J]. Nat Prod Commun 2014 9(4):529-532. |
[8] | WHEELER M C, GEKAKIS N.Hsp90 modulates PPARγ activity in a mouse model of non-alcoholic fatty liver disease[J]. J Lipid Res 2014,55(8): 1702-1710. |
[9] | SANTORO M, GUIDO C, DEAMICIS F, et al.Sperm metabolism in pigs: a role for peroxisome proliferator-activated receptor gamma (PPARgamma)[J]. J Exp Biol, 2013, 216(6):1085-1092. |
[10] | NAGY L, SZANTO A, SZATMARI I, et al.Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response[J]. Am Physiol Soc, 2011, 92(2):739-789. |
[11] | HAYDON R C, LUU H H, HE T C.Osteosarcoma and osteoblastic differentiation: a new perspective on oncogenesis[J]. Clinical Orthopaedics and Related Research,2007,454:237-246. |
[12] | SCHAEFER K L,W ADA K, TAKAHASHI H, et al. Peroxisome proliferator-activated receptor γ inhibition prevents adhesion to the extracellular matrix and induces anoikis in hepatocellular carcinoma cells[J]. Cancer Res, 2005, 65:2251-2259. |
[13] | GILL J, AHLUWALIA M K, GELLER D, et al.New targets and approaches in osteosarcoma[J]. Pharmacol Ther,2013,137:89-99. |
[14] | TAKAHASHI-YANAGA F, SASAGURI T GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy[J]. Cellular Signalling, 2008,20(4): 581-589. |
[15] | BURNS B S, EDIN M L, LESTER G E, et al.Selective drug resistant human osteosarcoma cell lines[J]. Clinical Orthopaedics and Related Research,2001,383:259-267. |
[16] | ISSEMANN I,GREEN S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators[J].Nature,1990,347(6294): 645-650. |
[17] | APOSTOLI A J, SKELHORNE-GROSS G E, RUBINO R E, et al. Loss of PPARγ expression in mammarysecretory epithelial cells creates a pro-breast tumorigenic environment[J].International Journal of Cancer,2014,134(5):1055-1066. |
[18] | KUMAR A P, LOO S Y, SHIN S W, et al. Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma[J].Antioxidants & Redox Signaling,2013 Nov 14. |
[19] | TORCHIA J, GLASS C, ROSENFELD M G.Co-activators and co-repressors in the integration of transcriptional responses[J]. Current Opinion in Cell Biology,1998,10(3):373-383. |
[20] | 徐飞,任晔,宫晨,等.PPARγ激动剂对MG-63细胞分泌OPG/RANKL的影响[J].骨科,2014,5(1):4-5. |