TFF3激活PI3K/Akt通路参与宫颈腺癌的发病机制
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摘要
目的:探讨TFF3通过激活PI3K/Akt信号通路调控宫颈腺癌发生发展的机制。方法:TFF3细胞因子和PI3K/Akt信号通路抑制剂(LY294002)或两者共同处理Hela细胞,CCK-8法检测Hela细胞增殖能力,Transwell小室观察细胞迁移能力,流式细胞学方法检测细胞凋亡,Western blot检测PI3K/Akt信号通路关键蛋白Akt及其激活状态蛋白p-Akt的表达。结果:与对照组相比,TFF3处理后Hela细胞的增殖和迁移能力明显提高,细胞凋亡减弱,差异有统计学意义(P<0.05);LY294002处理后Hela细胞的增殖及迁移能力明显降低,细胞凋亡增多,差异有统计学意义(P<0.05);TFF3+LY294002处理后Hela细胞的增殖、迁移能力及细胞凋亡与TFF3和LY294002处理组比较,差异均有统计学意义(P<0.05)。Western blot结果表明,TFF3能激活p-Akt基因表达。结论:TFF3能通过提高p-Akt蛋白表达激活PI3K/Akt信号通路,从而参与调节宫颈腺癌细胞的恶性行为。
Objective:To explore trefoil factor 3(TFF3) wether participate in the malignant process of cervical adenocarcinoma through PI3K/Akt signal pathway activaion.Methods:Hela cells were dealed with TFF3 and the inhibitor of PI3K/Akt signal pathway(LY294002).The cell counting Kit-8(CCK-8)assay was used to evaluate cell proliferation,and Transwell chamber assay was used to measure cell migration.Cell apoptosis was evaluated by Flow Cytometric assay.Western blot was used for testing the expression of p-Akt and Akt.Results:Compared with control group,the proliferation and migration of Hela cells were obviously enhanced when treated with TFF3(P<0.05),while these abilities were weakened when cells were treated with LY294002(P<0.05),the effection of co-treated group was in between(P<0.05).And the expression of p-Akt was significantly increased after TFF3 disposing Hela cells.Conclusion:TFF3 could activate PI3K/Akt signal pathway to regulate the pathogenesis of cervical adenocaicinoma.
Objective:To explore trefoil factor 3(TFF3) wether participate in the malignant process of cervical adenocarcinoma through PI3K/Akt signal pathway activaion.Methods:Hela cells were dealed with TFF3 and the inhibitor of PI3K/Akt signal pathway(LY294002).The cell counting Kit-8(CCK-8)assay was used to evaluate cell proliferation,and Transwell chamber assay was used to measure cell migration.Cell apoptosis was evaluated by Flow Cytometric assay.Western blot was used for testing the expression of p-Akt and Akt.Results:Compared with control group,the proliferation and migration of Hela cells were obviously enhanced when treated with TFF3(P<0.05),while these abilities were weakened when cells were treated with LY294002(P<0.05),the effection of co-treated group was in between(P<0.05).And the expression of p-Akt was significantly increased after TFF3 disposing Hela cells.Conclusion:TFF3 could activate PI3K/Akt signal pathway to regulate the pathogenesis of cervical adenocaicinoma.
引文
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[17] Vestergaard EM,Borre M,Poulsen SS,et al.Plasma levels of trefoil factors are increased in patients with advanced prostate cancer[J].Clin Cancer Res,2006,12(3 Pt 1):807-812
[18] Qu Y,Yang YIE,Ma D,et al.Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer[J].Oncol Rep,2012,27(4):1277-1283
[19] Yusup A,Huji B,Fang C,et al.Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis[J].World J Gastroenterol,2017,23(1):110-120
[20] Taniguchi Y,Kurokawa Y,Takahashi T,et al.Prognostic value of trefoil factor 3 expression in patients with gastric cancer[J].World J Surg,2018,42(12):3997-4004
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[22] Wang Q,Ma C,Kemmner W.Wdr66 is a novel marker for risk stratification and involved in epithelial-mesenchymal transition of esophageal squamous cell carcinoma[J].BMC Cancer,2013,13:137
[2] Pirog EC.Cervical adenocarcinoma:diagnosis of human papillomavirus-positive and human papillomavirus-negative tumors[J].Arch Pathol Lab Med,2017,141(12):1653-1667
[3] Molijn A,Chen W,Zhang X,et al.The complex relationship between human papillomavirus and cervical adenocarcinoma[J].Int J Cancer,2016,138(2):409-416
[4] Pirog EC.Cervical adenocarcinoma:diagnosis of human papillomavirus-positive and human papillomavirus-negative tumors[J].Arch Pathol Lab Med,2017,141(12):1653-1667
[5] Huang Z,Zhang X,Lu H,et al.Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening:A monocentric cohort study in China[J].BMC Gastroenterol,2014,14(1):74
[6] Pandey V,Zhang M,Li R,et al.Trefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma[J].Breast Cancer Res,2014,16(5):429-448
[7] You ML,Chen YJ,Chong QY,et al.Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent[J].Oncotarget,2017,8 (24):39323-39344
[8] Ailawadhi S,Nagase H,Khoury T,et al.Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma[J].Hepato-gastroenterol,2007,54(77):1339-1344
[9] Kosriwong K,Menheniott TR,Giraud AS,et al.Trefoil factors:Tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma[J].WJG,2011,17(12):1631-1641
[10] Sun Z,Liu H,Yang Z,et al.Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage[J].Int J Oncol,2014,45(3):1123-1132
[11] Lin J,Sun Z,Zhang W,et al.Protective effects of intestinal trefoil factor (ITF) on gastric mucosal epithelium through activation of extracellular signal-regulated kinase 1/2 (ERK1/2)[J].Mol Cell Biochem,2015,404(1-2):263-270
[12] Wang XN,Wang SJ,Pandey V,et al.Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and squamous cell carcinoma[J].Med (Baltimore),2015,94 (20):e860
[13] Sasieni P,Castanon A,Cuzick J.Screening and adenocarcinoma of the cervix[J].Int J Cancer,2009,125(3):525-529
[14] Pirog EC,Park KJ,Kiyokawa T,et al.Gastric-type adenocarcinoma of the cervix:tumor with wide range of histologic appearances[J].Adv Anatomic Pathol,2018,26(1):1-12
[15] Kim YW,Bae SM,Kim YW,et al.Target-based molecular signature characteristics of cervical adenocarcinoma and squamous cell carcinoma[J].Int J Oncol,2013,43(2):539-547
[16] Rinnert M,Hinz M,Buhtz P,et al.Synthesis and localization of trefoil factor family (TFF) peptides in the human urinary tract and TFF2 excretion into the urine[J].Cell and tissue research,2010,339 (3):639-647
[17] Vestergaard EM,Borre M,Poulsen SS,et al.Plasma levels of trefoil factors are increased in patients with advanced prostate cancer[J].Clin Cancer Res,2006,12(3 Pt 1):807-812
[18] Qu Y,Yang YIE,Ma D,et al.Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer[J].Oncol Rep,2012,27(4):1277-1283
[19] Yusup A,Huji B,Fang C,et al.Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis[J].World J Gastroenterol,2017,23(1):110-120
[20] Taniguchi Y,Kurokawa Y,Takahashi T,et al.Prognostic value of trefoil factor 3 expression in patients with gastric cancer[J].World J Surg,2018,42(12):3997-4004
[21] Tarca AL,Lauria M,Unger M,et al.Strengths and limitations of microarray-based phenotype prediction:lessons learned from the IMPROVER diagnostic signature challenge[J].Bioinformatics (Oxford,England),2013,29(22):2892-2899
[22] Wang Q,Ma C,Kemmner W.Wdr66 is a novel marker for risk stratification and involved in epithelial-mesenchymal transition of esophageal squamous cell carcinoma[J].BMC Cancer,2013,13:137