| 刘小慧,贺曼曼,郭明海,冯运章,张 伟,赵国杰.RNAi沉默SDF-1基因对人胃癌裸鼠原位移植瘤生物学行为的影响及机制[J].,2019,19(17):3250-3256 |
| RNAi沉默SDF-1基因对人胃癌裸鼠原位移植瘤生物学行为的影响及机制 |
| Effect of RNAi Silencing SDF-1 Gene on Biological Behavior of Orthotopic Transplanted human Gastric in Nude Mice and its Mechanism |
| 投稿时间：2019-03-03 修订日期：2019-03-27 |
| DOI：10.13241/j.cnki.pmb.2019.17.010 |
| 中文关键词: 基质细胞衍生因子-1 RNA干扰 胃癌 SGC7901细胞 裸鼠 生物学行为 |
| 英文关键词: SDF-1 RNA interference Gastric cancer SGC7901 cell Nude mice Biological behavior |
| 基金项目:河北省重点研发计划自筹项目（172777201） |
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| 中文摘要: |
| 摘要 目的：探讨RNAi技术沉默基质细胞衍生因子-1（stromal cell-derived factor-1，SDF-1）对人胃癌裸鼠原位移植瘤生物学行为的影响及可能机制。方法：利用RNAi-SDF-1细胞及对照组细胞建立人胃癌裸鼠皮下移植瘤，Western Blot检测裸鼠皮下移植瘤SDF-1蛋白表达情况。利用裸鼠皮下移植瘤建立其原位移植瘤模型，8周后处死裸鼠解剖尸体，检测原位移植瘤生长、凋亡及远处脏器转移情况。Western Blot检测SDF-1沉默对通路蛋白Akt、p-Akt、NF-κB、p-NF-κB以及侵袭转移相关基因E-cadherin、MMP-7表达的影响。结果：成功建立RNAi-SDF-1裸鼠原位移植瘤模型。与空白及阴性对照组比较，RNAi-SDF-1组裸鼠原位移植瘤生长缓慢，体积与质量均明显降低，差异有统计学意义（P<0.01）。流式细胞术结果显示，RNAi-SDF-1组肿瘤细胞凋亡率明显高于空白及阴性对照组（P<0.01）。尸体解剖结果显示，RNAi-SDF-1组肿瘤腹腔淋巴结及肝脏转移率明显低于空白及阴性对照组（P<0.05）。Western Blot结果显示，与空白及阴性对照组比较，RNAi-SDF-1组肿瘤组织中Akt、p-Akt、NF-κB、p-NF-κB、MMP-7表达水平明显降低，E-cadherin表达水平明显升高（P<0.01）。结论：RNAi-SDF-1能够有效抑制人胃癌SGC7901细胞裸鼠原位移植瘤的生长，诱导肿瘤细胞凋亡，抑制其腹腔淋巴结、肝脏转移，其机制可能与抑制PI3K-Akt、NF-κB信号通路及MMP-7的表达并上调E-cadherin的表达相关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of RNAi silencing stromal cell derived factor-1 (SDF-1) on the biological behavior of orthotopic transplanted human gastric cancer in nude mice and its possible mechanism. Methods: The subcutaneous transplanted tumor models of human gastric cancer in nude mice were constructed by using RNAi-SDF-1 cells and control cells, and the protein expression of SDF-1 in subcutaneous transplanted tumor of nude mice was detected by Western Blot. The orthotopic transplanted tumor model was established by using subcutaneous transplanted tumor in nude mice, and eight weeks later, the nude mice were dissected to detect the growth, apoptosis and distant organ metastasis of orthotopic transplanted tumor. The effects of SDF-1 silencing on the expression of pathway proteins Akt, p-Akt, NF-κB, p-NF-κB and invasion and metastasis related genes E-cadherin and MMP-7 were detected by Western Blot. Results: The orthotopic transplanted tumor model of RNAi-SDF-1 nude mice was successfully established. Compared with the blank and negative control group, the growth of orthotopic transplanted tumor in RNAi-SDF-1 group was slower, and the volume and mass of orthotopic transplanted tumor were significantly lower than those in blank and negative control group(P<0.01). The results of flow cytometry showed that the apoptosis rate of tumor cells in RNAi-SDF-1 group was significantly higher than that in blank and negative control groups(P<0.01). The results of autopsy showed that the metastasis rate of abdominal lymph nodes and liver in RNAi-SDF-1 group was significantly lower than that in blank and negative control groups(P<0.05). The results of Western Blot showed that the expression levels of Akt, p-Akt, NF-κB, p-NF-κB and MMP-7 in RNAi-SDF-1 group were significantly lower than those in blank and negative control groups, while the expression levels of E-cadherin were significantly higher than those in blank and negative control groups(P<0.01). Conclusion: RNAi-SDF-1 can effectively inhibit the growth of orthotopic transplanted tumor of human gastric cancer SGC7901 cells in nude mice, induce apoptosis of tumor cells, and inhibit the metastasis of abdominal lymph nodes and liver. The mechanism may be related to the inhibition of PI3K-Akt, NF-κB signaling pathway and MMP-7 expression and up-regulation of E-cadherin expression. |
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