文章摘要
江旭林,范星,汤俊,等.白细胞介素 22对结肠癌细胞增殖、迁移、侵袭和上皮间质转化的影响及作用机制[J].安徽医药,2020,24(11):2161-2165.
白细胞介素 22对结肠癌细胞增殖、迁移、侵袭和上皮间质转化的影响及作用机制
Effectand mechanism of IL?22 onthe proliferation,migration, invasion and epithelial?mesenchymal transition of colon cancer cells
  
DOI:10.3969/j.issn.1009?6469.2020.12.011
中文关键词: 结肠肿瘤  白细胞介素 22  蛋白激酶 B  增殖  迁移  侵袭
英文关键词: Colonic neoplasms  Interleukin 22  Protein kinase B  Proliferation  Migration  Invasion
基金项目:国家自然科学基金项目(81372323)
作者单位E-mail
江旭林 鄂州市中心医院胃肠外科湖北鄂州 436000  
范星 鄂州市中心医院胃肠外科湖北鄂州 436000  
汤俊 鄂州市中心医院胃肠外科湖北鄂州 436000  
陈校力 鄂州市中心医院胃肠外科湖北鄂州 436000  
严伟 鄂州市中心医院胃肠外科湖北鄂州 436000  
罗庆伟 鄂州市中心医院胃肠外科湖北鄂州 436000  
李志红 鄂州市中心医院胃肠外科湖北鄂州 436000 2475568754@qq.com 
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中文摘要:
      目的探讨白细胞介素 22(IL?22)对结肠癌细胞增殖、迁移、侵袭和上皮间质转化(EMT)的影响以及作用机制。方法收集鄂州市中心医院 2017年 1月至 2019年 1月接收的经病理诊断为结肠癌的病人 67例,经手术获取结肠癌组织和正常癌旁组织,免疫组织化学染色检测其中的 IL?22表达情况;用浓度分别为 10 μg/L、20 μg/L、40 μg/L的重组人 IL?22处理结肠癌 SW480细胞,以未经任何处理的 SW480细胞作为对照组; 40 μg/L的重组人 IL?22处理 SW480细胞后再用磷脂酰肌醇 3激酶(PI3K)/蛋白激酶 B(AKT)通路抑制剂 LY294002处理作为 IL?22+LY294002组。蛋白质印迹法(Western Blot)检测各组细胞蛋白表达;四甲基偶氮唑盐比色法(MTT)检测细胞增殖率; Transwell检测细胞侵袭和迁移。结果相较于癌旁组织,结肠癌组织中 IL?22阳性细胞表达率升高[(76.12±8.47)%比(28.35±4.21)%,t=41.340,P<0.001];相较于对照组,三个不同浓度 IL?22处理组结肠癌 SW480细胞增殖率升高[(36.72±5.47)%、(115.67±10.48)%、(166.42±11.81)%比(0.00±2.06)%,F=720.225,P< 0.001]Ki67蛋白表达水平升高[(0.77±0.08)、(0.84±0.11)(0.98±0.12)比(0.42±0.05)F=57.720,P<0.001];迁移细胞数升[(123.79,±8.64)个、(163.79±11.85)个、(223.79±15.72)个比(80.96±6.53)个, F=263.230,P,<0.001]侵袭细胞数升高[(94.65± 11.13)个、(134.71±9.54)个、(154.27±12.78)个比(57.35±7.83)个, F=152.287,P<0.001],MMP?2蛋白,表达水平升高[(0.71± 0.06)、(0.94±0.07)、(1.25±0.08)比(0.46±0.03)F=257.772,P<0.001];磷酸化蛋白激酶 B(p?AKT)蛋白表达水平升高[(0.42± 0.05)、(0.58±0.06)、(0.66±0.08)比(0.28±0.03),F=76.925,P<0.001];总 AKT(total?AKT)蛋白表达水平升高[(0.63±0.04)、(0.68±0.06)、(0.72±0.05)比(0.56±0.05),F=16.7,94,P<0.001]; E?cadherin表达水平降低[(0.31±0.04)、(0.19±0.03)、(0.15± 0.04)比(0.42±0.05)F=81.591,P<0.001],Vimentin表达水平升高[(0.45±0.05)、(0.61±0.05)、(0.77±0.08)比(0.39±0.03)F= 85.366,P<0.001]N?c,adherin表达水平升高[(0.51±0.06)、(0.58±0.07)、(0.71±0.08)比(0.45±0.03)F=28.462,P<0.001]。与,IL?22组相比, IL?22+,LY294002组结肠癌 SW480细胞中细胞增殖率降低[(141.69±13.58)%比(216.,64±17.36)%,P<0.001], Ki67蛋白表达水平降低[(0.68±0.07)比(0.94±0.09),P<0.001];迁移细胞数降低[(147.64±12.52)个比(246.19±18.56)个, P< 0.001];侵袭细胞数降低[(97.45±11.68)个比(148.46±13.48)个, P<0.001]; MMP?2蛋白表达水平降低[(0.74±0.08)比(1.13±0.11),P<0.001]; E?cadherin表达水平升高[(0.33±0.04)比(0.19±0.03),P<0.001]; Vimentin表达水平降低[(0.54±0.08)比(0.75±0.08),P<0.001]; N?cadherin表达水平降低[(0.55±0.06)比(0.68±0.07),P<0.001]。结论 IL?22可促进结肠癌 SW480细胞的增殖、迁移、侵袭和 EMT,其机制可能与 PI3K/AKT通路有关。
英文摘要:
      Objective To investigate the effects of interleukin 22(IL?22)on the proliferation,migration,invasion and epithelial? mesenchymal transition(EMT)of colon cancer cells and its mechanism.Methods The colon cancer tissues and adjacent tissues were collected,and the expressions of IL?22 in colon cancer tissues and paracancerous tissues were detected by immunohistochemi?cal staining.SW480 cells were treated with recombinant human IL?22 at the concentrations of 10 μg/L,20 μg/L,and 40 μg/L,re? spectively,with SW480 cells without any treatment as a control group. SW480 cells treated with 40 μg/L recombinant human IL?22were then treated with the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)pathway inhibitor LY294002,as the IL?22+ LY294002 group.Western Blot was used to detect protein expression.Methyl thiazolyl tetrazolium(MTT)was used to detect cell proliferation rate and Transwell was used to detect cell invasion and migration.Results Compared with adjacent tissues,the expres? sion rate of IL?22 positive cells in colon cancer tissues was increased[(76.12±8.47)% vs.(28.35±4.21)%,t=41.340,P<0.001]. In the three different IL?22 treatment groups,compared with the control group,the proliferation rates of colon cancer SW480 cells were increased[(36.72±5.47)%,(115.67±10.48)%,(166.42±11.81)% vs.(0.00±2.06)%,F=720.225,P<0.001],the expression of Ki67 protein was increased[(0.77±0.08),(0.84±0.11),(0.98±0.12)vs.(0.42±0.05),F=57.720,P<0.001]; the number of mi? grating cells was increased[(123.79±8.64),(163.79±11.85),(223.79±15.72)vs.(80.96±6.53),F=263.230,P<0.001],the num? ber of invading cells was increased[(94.65±11.13),(134.71±9.54),(154.27±12.78)vs.(57.35±7.83),F=152.287,P<0.001]; the expression level of MMP?2 protein was increased[(0.71±0.06)(0.94±0.07),(1.25±0.08)vs.(0.46±0.03)F=257.772,P< 0.001];thee xpression level of phosphorylatedproteinkinaseB(p?AKT,)protein was increased[(0.42±0.05)(0.58,±0.06)(0.66± 0.08)vs.(0.28±0.03)F=76.925,P<0.001]; the expression of total AKT protein was increased[(0.63±0.04),,(0.68±0.,06),(0.72±0.05)vs.(0.56±0.,05)F=16.794,P<0.001]; E?cadherin expression was decreased[(0.31±0.04),(0.19±0.03),(0.15± 0.04)vs.(0.42±0.05)F=81.59,1,P<0.001],the expression of Vimentin was increased[(0.45±0.05)(0.61±0.05)(0.77±0.08) vs.(0.39±0.03),F=85.,366,P<0.001],and N?cadherin expression was increased[(0.51±0.06)(0.58,±0.07),(0.71,±0.08)vs.(0.45±0.03),F=28.462,P<0.001].Compared with the IL?22 group, n cancer SW480 cells in the IL?22+LY294002 group was reduced[(141.69±13.58)% vs.(216.64±17.36)%,P<0.001]; the number of migrating cells was de? creased[(147.64±12.52) vs.(246.19±18.56), P<0.001]; the number of invasive cells was decreased[(97.45±11.68) vs.thecellproliferationrateofcolo,(148.46±13.48),P<0.001]; MMP?2 protein expression was decreased[(0.74±0.08)vs.(1.13±0.11),P<0.001]; E?cadherin ex? pression was increased[(0.33±0.04)vs.(0.19±0.03),P<0.001]; Vimentin expression was decreased[(0.54±0.08)vs.(0.75±0.08),P<0.001]; N?cadherin expression was decreased[(0.55±0.06)vs.(0.68± 0.07),P<0.001].Conclusion IL?22 can pro? mote the proliferation,migration,invasion and EMT of SW480 cells,and its mechanism may be related to PI3K/AKT pathway.
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