miR-155靶向PTEN-PI3KAKT通路促进鼻咽癌细胞增殖并抑制其凋亡的实验研究

miR-155 Targeting the Pten-pi3kakt Pathway Promotes the Proliferation of Nasopharyngeal Carcinoma Cells and Inhibits Their Apoptosis

目的:研究miR-155靶向PTEN-PI3KAKT通路促进鼻咽癌细胞增殖并抑制其凋亡的作用机制。方法:选取105只成年健康SD雄性大鼠作为研究对象,将其以随机抽签法等分成观察组、对照组、试验组,每组35只。所有大鼠通过诱癌剂二甲硝基哌嗪腋部皮下注射以及促癌剂佛波醇酯皮下注射进行鼻咽癌大鼠模型的建立。观察组大鼠予以miR-155抑制剂干预,试验组予以PI3K抑制剂干预,对照组不予以任何干预。以实时荧光定量PCR法检测miR-155相对表达量,采用免疫组化法检测PTEN、PI3K、P-AKT表达情况,通过Western blot法检测Bcl-2、Bax、Ezrin蛋白表达水平。比较三组大鼠上述相关指标水平,并作相关性分析。结果:试验组、观察组、对照组大鼠的miR-155相对表达量分别为(34.88±1.32)、(29.72±1.23)、(35.01±1.34),观察组显著低于试验组和对照组,差异明显(F=23.105,P=0.000)。试验组、观察组、对照组大鼠PTEN表达率逐渐升高,而PI3K、P-AKT表达率逐渐降低(均P<0.05)。经Pearson相关性分析可得:鼻咽癌大鼠miR-155相对表达量与PTEN表达率呈正相关关系,而与PI3K、P-AKT表达率呈负相关关系(均P<0.05)。试验组、观察组、对照组Bcl-2、Ezrin蛋白表达水平呈逐渐升高趋势,而Bax蛋白表达水平呈逐渐减低趋势,且经单因素方差分析发现:各组间对比差异显著(均P<0.05)。结论:miR-155可能是通过靶向作用于PTEN-PI3KAKT信号通路,继而发挥促进鼻咽癌细胞增殖以及抑制鼻咽癌细胞凋亡的作用。临床工作中可能将其作为鼻咽癌治疗的新靶点。

Objective:To investigate and analyze the mechanism of miR-155 targeting pten-pi3kakt pathway to promote the proliferation and inhibit the apoptosis of nasopharyngeal carcinoma cells.Methods:105 healthy adult SD male rats were selected as research objects,and they were divided into observation group and control group and experimental group by random draw method,with 35 rats in each group.The rat model of nasopharyngeal carcinoma was established by subcutaneous injection of cancer inducer dimethylenitropiperazine in the axils and progenitor phopol.The observation group was given mir-155 inhibitor intervention,the experimental group was given PI3K inhibitor intervention,and the control group was not given any intervention.The relative expressions of mir-155 were detected by real-time fluorescence quantitative PCR,the expressions of PTEN,PI3K and p-akt were detected by immunohistochemistry,and the expression levels of bcl-2,Bax and Ezrin were detected by Western blot.The three groups of rats were compared and the correlation was analyzed.Results:The relative expression levels of mir-155 in the experimental group,the observation group and the control group were(34.88±1.32),(29.72±1.23)and(35.01±1.34),respectively,which were significantly lower in the observation group than in the experimental group and the control group(F=23.105,P=0.000).The expression rate of PTEN in experimental group,observation group and control group increased gradually,while the expression rate of PI3K and p-akt decreased gradually(all P<0.05).Pearson correlation analysis showed that the relative expression level of miR-155 in nasopharyngeal carcinoma rats was positively correlated with the expression rate of PTEN,but negatively correlated with the expression rate of PI3K and p-akt(all P<0.05).The expression levels of bcl-2 and Ezrin in the experimental group,the observation group and the control group showed a trend of gradual increase,while the expression levels of Bax protein showed a trend of gradual decrease.Moreover,one-way anova showed that there were significant differences among the groups(all P<0.05).Conclusion:MiR-155 may play a role in promoting the proliferation of nasopharyngeal carcinoma cells and inhibiting the apoptosis of nasopharyngeal carcinoma cells by targeting the pten-pi3kakt signaling pathway.It may be a new target in the treatment of nasopharyngeal carcinoma.