MMP-9抑制剂通过PI3K/Akt信号通路对人口腔鳞癌SCC15细胞株生物学行为的影响  

Influence of MMP-9 inhibitor on biological behaviors of SCC15 cells through PI3K/Akt signaling pathway

作　　者：何伟[1] 刘世杰[1] 韩永洁[1] 王云[1] HE Wei;LIU Shijie;HAN Yongjie;WANG Yun(Department of Maxillofacial Surgery,Qinghai People’s Hospital,Xining 810007,China)

机构地区：[1]青海省人民医院颌面外科,西宁810007

出　　处：《中华实用诊断与治疗杂志》2020年第8期805-809,共5页Journal of Chinese Practical Diagnosis and Therapy

基　　金：青海省基础研究计划项目(2018-0302-ZJC-0041)。

摘　　要：目的探讨基质金属蛋白酶-9(matrix metalloproteinase-9, MMP-9)抑制剂(SB-3CT)通过磷脂酰肌醇-3激酶(phosphatidylinositol-3 kinase, PI3K)/蛋白激酶B(protein kinase B, Akt)信号通路对人口腔鳞癌SCC15细胞株增殖、侵袭、迁移的调控作用。方法对数生长期SCC15细胞分为对照组、低剂量组、中剂量组和高剂量组,分别采用0、2.5、5、10μmol/L SB-3CT进行处理。采用MTT法检测处理24、48、72 h时细胞增殖率;处理24 h时,采用Transwell小室试验检测侵袭细胞数,采用划痕试验检测细胞融合距离,采用实时荧光定量PCR法检测细胞MMP-9、PI3K、Akt mRNA相对表达量,采用Western blot法检测细胞MMP-9、PI3K、Akt、p-Akt蛋白相对表达量。结果处理24、48、72 h时,低、中、高剂量组细胞增殖率低于对照组(P<0.05),低、中、高剂量组细胞增殖率依次降低(P<0.05),低、中、高剂量组细胞增殖率均随处理时间延长而降低(P<0.05)。处理24 h时,低、中、高剂量组侵袭细胞数[(96.26±21.11)、(52.00±13.13)、(21.20±6.15)个]和细胞融合距离[(91.80±25.00)、(65.10±19.00)、(27.20±11.00)μm]小于对照组[(125.00±31.15)个、(127.90±27.00)μm](P<0.05),低、中、高剂量组依次减小(P<0.05)。低、中、高剂量组细胞MMP-9、PI3K mRNA和MMP-9、PI3K、p-Akt蛋白相对表达量及p-Akt/Akt明显低于对照组(P<0.05),低、中、高剂量组依次降低(P<0.05)。4组细胞Akt mRNA和蛋白相对表达量比较差异无统计学意义(P>0.05)。结论 MMP-9抑制剂可抑制人口腔鳞癌SCC15细胞的增殖、侵袭和迁移能力,可能通过PI3K/Akt信号通路发挥调控作用。Objective To investigate the role of matrix metalloproteinase-9(MMP-9) inhibitor(SB-3 CT) on regulating the proliferation, invasion and migration of human oral squamous cell carcinoma SCC15 cell line through phosphatidylinositol-3 kinase(PI3 K)/protein kinase B(Akt) signaling pathway. Methods SCC15 cells were divided into control, low-dose, medium-dose and high-dose groups, treated with 0, 2.5, 5 and 10 μmol/L SB-3 CT, respectively. MTT method was used to detect the proliferation rate after treatment for 24, 48 and 72 h. After treatment for 24 h, Transwell and scratch assays were used to detect the number of invasive cells and the fusion distance of cells, real-time fluorescence quantitative PCR was used to detect the relative expressions of MMP-9, PI3 K and Akt mRNA, and Western blot was used to detect the relative expressions of MMP-9, PI3 K, Akt and p-Akt proteins in each group. Results After treatment for 24, 48 and 72 h, the cells proliferation rate deceased gradually in low-dose group, medium-dose group, high-dose group and control group in turn(P<0.05), and decreased with the extensien of treatment time in low-, medium-and high-dose groups(P<0.05). After treatment for 24 h, the number of invasive cells and the fusion distance decreased gradually in control group(125.00±31.15,(127.90±27.00) μm), low-dose group(96.26±21.11,(91.80±25.00) μm), medium-dose group(52.00±13.13,(65.10±19.00) μm) and high-dose group(21.20±6.15,(27.20±11.00) μm)(P<0.05). The relatives expressions of MMP-9 mRNA, PI3 K mRNA, MMP-9 protein, PI3 K protein,p-Akt protein and p-Akt/Akt decreased gradually in control group,low-dose group,medium-dose group and high-dose group in turn(P<0.05).There were no significant differences in the relative expressions of Akt mRNA and protein among four groups(P>0.05).Conclusion MMP-9 inhibitor could inhibit the proliferation,invasion and migration of human oral squamous cell carcinoma SCC15 cell line probably through PI3 K/Akt signaling pathway.

关 键 词：人口腔鳞癌 基质金属蛋白酶-9 磷脂酰肌醇-3激酶 蛋白激酶B 侵袭 迁移 信号通路 

分 类 号：R739.8[医药卫生—肿瘤]