核基质结合蛋白SATB1对胃癌生物学行为的影响及其机制研究
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摘要
背景：胃癌是全世界排名第四个最普遍被诊断的癌症,而且死亡率排名第二,被视为危害人类健康最常见的恶性肿瘤之一。目前对于胃癌的发病和其出现侵袭转移的机制尚不明确。有研究发现核基质结合蛋白SATB1在部分肿瘤中表达异常,且在介导乳腺癌的侵袭转移中发挥关键性作用,表达SATB1的乳腺癌细胞的中SATB1被沉默抑制时,有侵袭转移能力的乳腺癌细胞丧失侵袭转移的能力；而本不具备侵袭转移能力的乳腺癌细胞转染SATB1基因使其高表达可以使乳腺癌细胞获得侵袭转移能力。提示SATB1在肿瘤的侵袭转移或者其它生物学功能中扮演重要角色。我们研究发现SATB1的胃癌中也存在异常表达,而且且表达水平与肝素酶的表达水平具有一致性。我们运用转录因子分析软件Mat-inspector发现,在肝素酶上游启动子区域中有8个高度可能与SATB1蛋白结合的位点,提示二者之间可能存在联系。
目的：明确SATB1在胃癌组织和胃癌细胞中的表达水平,明确SATB1的表达的变化对胃癌细胞生物学行为和肝素酶表达的影响,初步明确其在胃癌的发生和发展中的作用,为胃癌的诊断治疗提供新思路。
方法：免疫组化和RT-PCR检测胃癌组织和癌旁组织中SATB1蛋白和mRNA的表达水平；RT-PCR和Western Blot法检测不同侵袭能力细胞系(MDA-MB-435S、AGS、SGC-7901和GES-1)中SATB1 mRNA和蛋白的表达水平差异；构建SATB1的真核表达载体pcDNA3.0-SATB1,双酶切和细胞转染检测表达水平变化鉴定pcDNA3.0-SATB1,转染SGC-7901细胞48小时后,MTT法检测细胞增殖活性,流式细胞术检测转染前后细胞周期、凋亡水平变化,transwell小室法检测细胞侵袭能力变化,RT-PCR和Western Blot法检测转染前后细胞肝素酶表达水平的变化；设计SATB1的aiRNA和siRNA干扰序列,转染AGS细胞48小时后,MTT法检测细胞增殖活性,流式细胞术检测转染前后细胞周期、凋亡水平变化,transwell小室法检测细胞侵袭能力变化,RT-PCR和Western Blot法检测转染前后细胞肝素酶表达水平的变化。
结果：免疫组化显示SATB1在胃癌组织中呈高阳性表达,48例胃癌标本中有41例为阳性表达,阳性率为85.42%(41／48),癌旁组织中阳性率为4.17%(2／48),胃癌组织中SATB1蛋白表达明显上调(p<0.01)；RT-PCR显示,胃癌组织中出现SATB1 mRNA表达的阳性率为87.50%(42／48),对应的癌旁组织阳性率为6.25%(3／48),胃癌组织组织与癌旁组织比较有统计学差异(p<0.01)；RT-PCR显示,MDA-MB-435S、AGS、SGC-7901和GES-1四组细胞SATB1/β-actin比值依次为：0.437±0.021：0.269±0.017：0.019±0.006：0.011±0.003,高侵袭性的细胞系AGS中SATB1 mRNA的表达水平SGC-7901比较有统计学差异(p<0.01)；Western Blot发现SATB1蛋白在AGS细胞系中表达水平高于其在SGC-7901中表达水平(p<0.01)；双酶切鉴定真核表达载体pcDNA3.0-SATB1构建成功,SGC-7901细胞转染pcDNA3.0-SATB148小时后, RT-PCR检测pcDNA3.0-SATB1转染组和对照组SATB1/β-actin的比值分别为：0.537±0.028和0.098±0.007,pcDNA3.0-SATB1转染组与空白对照组比较有统计学差异(p<0.01),Western Blot结果显示pcDNA3,0-SATB1转染组和对照组SATB1/β-actin的比值分别为：0.196±0.013和0.067±0.008。pcDNA3.0-SATB1转染组与空白对照组SATB1的蛋白表达量比较有统计学差异(p<0.01),MTT结果显示转染SATB1可以促进SGC-7901细胞增殖,空白对照组、pcDNA3.0转染组和pcDNA3.0-SATB1转染组的各周期的分布分别为：(G0／G1：65.27±5.38、78.36±4.64、52.28±4.13；S：24.52±1.68、10.25±1.13、27.95±0.31;G2/M：10.21±1.13、11.39±0.96、19.77±1.02),pcDNA3.0-SATB1转染组G2/M比例增加(p<0.05),各组的凋亡百分比分别为：2.88±0.07、2.29±0.12和2.92±0.14,组间比较没有统计学差异(p>0.05),Transwell小室法检测各组SGC-7901细胞数目分别为：47.26±3.39、44.65±3.11和128.67±9.13,pcDNA3.0-SATB1转染组与空白对照组和空质粒组比较均有统计学差异(p<0.05),RT-PCR结果显示Heparanase/β-actin的比值分别为：0.154±0.017、0.169±0.011和3.46±0.018,pcDNA3.0-SATB1转染组的肝素酶表达水平与对照组和空质粒组比较均有统计学差异(p<0.05),Western Blot结果显示,SGC-7901细胞肝素酶(Heparanase)蛋白表达水平也同时上调,空白对照组、pcDNA3.0转染组和pcDNA3.0-SATB1转染组Heparanase/β-actin的比值分别为：0.108±0.008、0.113±0.009和2.25±0.016。pcDNA3.0-SATB1转染组的肝素酶蛋白表达水平与对照组和空质粒组比较均有统计学差异(p<0.05)；AGS细胞转染SATB1-siRNA或者SATB1-aiRNA后,SATB1mRNA表达水平明显下降,对照组、siRNA组和aiRNA组SATB1/β-actin的比值分别为：0.649±0.021、0.104±0.016和0.072±0.009。siRNA组和aiRNA组与对照组比较均有统计学差异(p<0.01),aiRNA组与siRNA组比较也有统计学差异(p<0.05),Western blot显示对照组、siRNA组和aiRNA组SATB1/β-actin的比值分别为：0.231±0.016、0.075±0.008和0.063±0.011,siRNA组和aiRNA组与对照组比较均有统计学差异(p<0.01),aiRNA组与siRNA组比较没有统计学差异(p<0.05),MTT结果显示抑制SATB1的表达可以抑制AGS细胞增殖,与对照组比较,siRNA组和aiRNA组G0／G1比例均出现不同程度的增加(p<0.05)；相应的S期和G2/M比例均出现下调(p<0.05),提示沉默SATB1的表达以后AGS细胞出现G0／G1阻滞,对照组、siRNA组和aiRNA组的凋亡百分比分别为：2.69±0.09、6.37±0.42和10.12±0.61,组间比较有统计学差异(p<0.05),Transwell小室法检测各组AGS细胞侵袭性发现,对照组、siRNA组和aiRNA组的细胞数目分别为：137.67±12.36、73.54±10.61和31.55±4.27,后两组与对照组比较有统计学差异(p<0.05),RT-PCR和Western blot结果显示,沉默SATB1的表达以后,AGS细胞肝素酶mRNA和蛋白表达水平均下调(p<0.05)。
结论：SATB1在胃癌组织中呈异常高表达,在高侵袭性的AGS胃癌细胞中表达水平高于低侵袭性的SGC-7901细胞；上调SATB1的表达能够促进SGC-7901细胞增殖,加快细胞进入活跃周期,增强SGC-7901细胞侵袭能力,增加肝素酶的表达水平；aiRNA能够有效地沉默SATB1的表达,沉默SATB1的表达后,AGS细胞增殖活性减弱,出现G0／G1阻滞,凋亡比例增加,细胞侵袭能力下降,肝素酶表达水平下调。显示SATB1可能参与胃癌的发生发展和侵袭转移,可能成为评价胃癌预后的重要指标之一,可能成为胃癌治疗的新靶点。
Background:Stomach cancer is the fourth most common cancer worldwide. It is a disease with a high death rate making it the second most common cause of cancer death worldwide after lung cancer. The mechanism of gastric cancer incidence、invasion and metastasis is still unclear. There is study reported that nuclear matrix protein SATB1 was abnormal expression in some tumor. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells reversed tumorigenesis by restoring breast-like acinar polarity and inhibited tumor growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SK-BR-3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 functions as a genome organizer during tumorigenesis to reprogramme expression and promote metastasis. Our studies have found that SATB1 was also abnormal expression in gastric cancer, and its expression was consistent with the expression of heparanase. We used transcription factor binding site analysis Software Mat-inspector and found that there are 8 sites in the upstream promoter region of heparanase may combine with SATB1 protein, indicating possible link between them.
Objective:investigate the expression of SATB1 in gastric cancer and Gastric cancer cell lines. Regulate the expression of SATB1 to know the changes in the biological behavior and the heparanase expression of gastric cancer cell line. It may provide new idea for the diagnosis and treatment of gastric cancer.
Method:Immunohistochemistry and RT-PCR detect the expression of SATB1 protein and mRNA in gastric cancer and adjacent tissues; RT-PCR and Western blot detect the expression of SATB1 mRNA and protein in MDA-MB-435S、AGS、SGC-7901 and GES-1 cell line. Construction the eukaryotic expression vector pcDNA3.0-SATB1 and DNA double restriction enzyme digestion identification of plasmid. After transient transfection of SGC-7901 cells 48 h, RT-PCR and Western blot detection the expression of SATB1 mRNA and protein; MTT assay detection the cell proliferation; Flow cytometry analysis of cell-cycle arrest and apoptosis; transwell chamber assay detection the cell invasion; RT-PCR and Western blot detection the expression of heparanase. Design and synthesis of SATB1 siRNA oligonucleotides, After transient transfection of AGS cells 48 h, RT-PCR and Western blot detection the expression of SATB1 mRNA and protein; MTT assay detection the cell proliferation; Flow cytometry analysis of cell-cycle arrest and apoptosis; transwell chamber assay detection the cell invasion; RT-PCR and Western blot detection the expression of heparanase.
Results:Immunohistochemical analysis of 48 gastric cancer samples showed that 41 samples were positively expressed and the positive rate was 85.42%(41/48), however, the positive rate was only 4.17%(2/48) in adjacent tissues. RT-PCR showed in cancer samples and adjacent tissues the positive expression of SATB1 mRNA were 87.50%(42/48) and 25 %(3/48), respectively (p<0.01). The SATB1/β-actin mRNA rate in MDA-MB-435S, AGS, SGC-7901 and GES-1 cell lines were 0.437±0.021; 0.269±0.017; 0.019±0.006 and 0.011±0.003, respectively. Western Blot showed that the expression of SATB1 protein in AGS cell was higher than that in SGC-7901 cell (p<0.01). After transient transfection of SGC-7901 cells 48 h, RT-PCR showed that the SATB1/β-actin mRNA was 0.537±0.028 in pcDNA3.0-SATB1 transfection group and 0.098±0.007 in blank control group(p<0.05). Western Blot showed the SATB1/β-actin protein was 0.196±0.013 in pcDNA3.0-SATB1 transfection group and 0.067±0.008 in blank control group (p<0.05). MTT assay showed the proliferation ability of the SGC-7901 cell line in pcDNA3.0-SATB1 transfection group was enhanced (p<0.05).Flow cytometry showed that cycle distribution (G0/G1, S, G2/M) of blank control group, pcDNA3.0 transfection group and pcDNA3.0-SATB1 transfection group were G0/G1:65.27±5.38,78.36±4.64,52.28±4.13; S:24.52±1.68,10.25±1.13, 27.95±0.31, G2/M:10.21±1.13,11.39±0.96,19.77±1.02, respectively; the rate of G2/M in pcDNA3.0-SATB1 group increased (p<0.05). The apoptosis rates of three group were similar (p>0.05). Transwell chamber assay showed that the cell in blank control group, pcDNA3.0 transfection group and pcDNA3.0-SATBl transfection group were 47.26±3.39, 44.65±3.11 and 128.67±9.13, respectively. The cell number in pcDNA3.0-SATB1 transfection group was higher than those of other two group (p<0.05). RT-PCR and Western Blot showed that the expression of heparanase was unregulated in pcDNA3.0-SATB1 transfection group (p<0.05). aiRNA transfection could effectively silence gene expression. When AGS cell was transfected with SATB1-siRNA or SATB1-aiRNA, the expression of SATB1 was down-regulated in both group compared with control group (p<0.05), and SATB1-aiRNA could more effectively silence SATB1 mRNA expression (p<0.05). MTT assay showed the proliferation of the AGS cell line in SATBl-siRNA and SATB1-aiRNA transfection group was inhibited (p<0.05). Flow cytometry showed that percentage of G0/G1 was increased in SATBl-siRNA and SATBl-aiRNA transfection group (p<0.05), indicating of G0/G1 arrest. The apoptosis rate in control, SATB1-siRNA and SATBl-aiRNA transfection group was 2.69±0.09,6.37±0.42,10.12±0.61, respectively (p<0.05). Transwell chamber assay showed that the cells in control group, SATB1-siRNA and SATB1-aiRNA transfection group were 137.67±12.36,73.54±10.61 and 31.55±4.27, respectively (p<0.05). RT-PCR and Western Blot showed that the expression of heparanase were both down-regulated in SATB1-siRNA and SATB1-aiRNA transfection group (p<0.05).
Conclusion:The SATB1 gene was high positive expression in gastric cancer, and the expression of SATB1 is higher in AGS cell line than in SGC-7901 cell line. Up-regulation the expression of SATB1 in SGC-7901 cell could induce the cell proliferation, accelerate cell cycle progression, enhance invasive potential, and increase the expression of heparanase; however, down-regulation the expression of SATB1 in AGS cell could inhibit the cell proliferation, induce G0/G1 cell cycle arrest and cell apoptosis, reduce invasive potential and decrease the expression of heparanase. SATB1 could be involved in the progression of gastric cancer. It may be a new important prognostic indicators and therapeutic target of gastric cancer.
目的：明确SATB1在胃癌组织和胃癌细胞中的表达水平,明确SATB1的表达的变化对胃癌细胞生物学行为和肝素酶表达的影响,初步明确其在胃癌的发生和发展中的作用,为胃癌的诊断治疗提供新思路。
方法：免疫组化和RT-PCR检测胃癌组织和癌旁组织中SATB1蛋白和mRNA的表达水平；RT-PCR和Western Blot法检测不同侵袭能力细胞系(MDA-MB-435S、AGS、SGC-7901和GES-1)中SATB1 mRNA和蛋白的表达水平差异；构建SATB1的真核表达载体pcDNA3.0-SATB1,双酶切和细胞转染检测表达水平变化鉴定pcDNA3.0-SATB1,转染SGC-7901细胞48小时后,MTT法检测细胞增殖活性,流式细胞术检测转染前后细胞周期、凋亡水平变化,transwell小室法检测细胞侵袭能力变化,RT-PCR和Western Blot法检测转染前后细胞肝素酶表达水平的变化；设计SATB1的aiRNA和siRNA干扰序列,转染AGS细胞48小时后,MTT法检测细胞增殖活性,流式细胞术检测转染前后细胞周期、凋亡水平变化,transwell小室法检测细胞侵袭能力变化,RT-PCR和Western Blot法检测转染前后细胞肝素酶表达水平的变化。
结果：免疫组化显示SATB1在胃癌组织中呈高阳性表达,48例胃癌标本中有41例为阳性表达,阳性率为85.42%(41／48),癌旁组织中阳性率为4.17%(2／48),胃癌组织中SATB1蛋白表达明显上调(p<0.01)；RT-PCR显示,胃癌组织中出现SATB1 mRNA表达的阳性率为87.50%(42／48),对应的癌旁组织阳性率为6.25%(3／48),胃癌组织组织与癌旁组织比较有统计学差异(p<0.01)；RT-PCR显示,MDA-MB-435S、AGS、SGC-7901和GES-1四组细胞SATB1/β-actin比值依次为：0.437±0.021：0.269±0.017：0.019±0.006：0.011±0.003,高侵袭性的细胞系AGS中SATB1 mRNA的表达水平SGC-7901比较有统计学差异(p<0.01)；Western Blot发现SATB1蛋白在AGS细胞系中表达水平高于其在SGC-7901中表达水平(p<0.01)；双酶切鉴定真核表达载体pcDNA3.0-SATB1构建成功,SGC-7901细胞转染pcDNA3.0-SATB148小时后, RT-PCR检测pcDNA3.0-SATB1转染组和对照组SATB1/β-actin的比值分别为：0.537±0.028和0.098±0.007,pcDNA3.0-SATB1转染组与空白对照组比较有统计学差异(p<0.01),Western Blot结果显示pcDNA3,0-SATB1转染组和对照组SATB1/β-actin的比值分别为：0.196±0.013和0.067±0.008。pcDNA3.0-SATB1转染组与空白对照组SATB1的蛋白表达量比较有统计学差异(p<0.01),MTT结果显示转染SATB1可以促进SGC-7901细胞增殖,空白对照组、pcDNA3.0转染组和pcDNA3.0-SATB1转染组的各周期的分布分别为：(G0／G1：65.27±5.38、78.36±4.64、52.28±4.13；S：24.52±1.68、10.25±1.13、27.95±0.31;G2/M：10.21±1.13、11.39±0.96、19.77±1.02),pcDNA3.0-SATB1转染组G2/M比例增加(p<0.05),各组的凋亡百分比分别为：2.88±0.07、2.29±0.12和2.92±0.14,组间比较没有统计学差异(p>0.05),Transwell小室法检测各组SGC-7901细胞数目分别为：47.26±3.39、44.65±3.11和128.67±9.13,pcDNA3.0-SATB1转染组与空白对照组和空质粒组比较均有统计学差异(p<0.05),RT-PCR结果显示Heparanase/β-actin的比值分别为：0.154±0.017、0.169±0.011和3.46±0.018,pcDNA3.0-SATB1转染组的肝素酶表达水平与对照组和空质粒组比较均有统计学差异(p<0.05),Western Blot结果显示,SGC-7901细胞肝素酶(Heparanase)蛋白表达水平也同时上调,空白对照组、pcDNA3.0转染组和pcDNA3.0-SATB1转染组Heparanase/β-actin的比值分别为：0.108±0.008、0.113±0.009和2.25±0.016。pcDNA3.0-SATB1转染组的肝素酶蛋白表达水平与对照组和空质粒组比较均有统计学差异(p<0.05)；AGS细胞转染SATB1-siRNA或者SATB1-aiRNA后,SATB1mRNA表达水平明显下降,对照组、siRNA组和aiRNA组SATB1/β-actin的比值分别为：0.649±0.021、0.104±0.016和0.072±0.009。siRNA组和aiRNA组与对照组比较均有统计学差异(p<0.01),aiRNA组与siRNA组比较也有统计学差异(p<0.05),Western blot显示对照组、siRNA组和aiRNA组SATB1/β-actin的比值分别为：0.231±0.016、0.075±0.008和0.063±0.011,siRNA组和aiRNA组与对照组比较均有统计学差异(p<0.01),aiRNA组与siRNA组比较没有统计学差异(p<0.05),MTT结果显示抑制SATB1的表达可以抑制AGS细胞增殖,与对照组比较,siRNA组和aiRNA组G0／G1比例均出现不同程度的增加(p<0.05)；相应的S期和G2/M比例均出现下调(p<0.05),提示沉默SATB1的表达以后AGS细胞出现G0／G1阻滞,对照组、siRNA组和aiRNA组的凋亡百分比分别为：2.69±0.09、6.37±0.42和10.12±0.61,组间比较有统计学差异(p<0.05),Transwell小室法检测各组AGS细胞侵袭性发现,对照组、siRNA组和aiRNA组的细胞数目分别为：137.67±12.36、73.54±10.61和31.55±4.27,后两组与对照组比较有统计学差异(p<0.05),RT-PCR和Western blot结果显示,沉默SATB1的表达以后,AGS细胞肝素酶mRNA和蛋白表达水平均下调(p<0.05)。
结论：SATB1在胃癌组织中呈异常高表达,在高侵袭性的AGS胃癌细胞中表达水平高于低侵袭性的SGC-7901细胞；上调SATB1的表达能够促进SGC-7901细胞增殖,加快细胞进入活跃周期,增强SGC-7901细胞侵袭能力,增加肝素酶的表达水平；aiRNA能够有效地沉默SATB1的表达,沉默SATB1的表达后,AGS细胞增殖活性减弱,出现G0／G1阻滞,凋亡比例增加,细胞侵袭能力下降,肝素酶表达水平下调。显示SATB1可能参与胃癌的发生发展和侵袭转移,可能成为评价胃癌预后的重要指标之一,可能成为胃癌治疗的新靶点。
Background:Stomach cancer is the fourth most common cancer worldwide. It is a disease with a high death rate making it the second most common cause of cancer death worldwide after lung cancer. The mechanism of gastric cancer incidence、invasion and metastasis is still unclear. There is study reported that nuclear matrix protein SATB1 was abnormal expression in some tumor. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells reversed tumorigenesis by restoring breast-like acinar polarity and inhibited tumor growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SK-BR-3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 functions as a genome organizer during tumorigenesis to reprogramme expression and promote metastasis. Our studies have found that SATB1 was also abnormal expression in gastric cancer, and its expression was consistent with the expression of heparanase. We used transcription factor binding site analysis Software Mat-inspector and found that there are 8 sites in the upstream promoter region of heparanase may combine with SATB1 protein, indicating possible link between them.
Objective:investigate the expression of SATB1 in gastric cancer and Gastric cancer cell lines. Regulate the expression of SATB1 to know the changes in the biological behavior and the heparanase expression of gastric cancer cell line. It may provide new idea for the diagnosis and treatment of gastric cancer.
Method:Immunohistochemistry and RT-PCR detect the expression of SATB1 protein and mRNA in gastric cancer and adjacent tissues; RT-PCR and Western blot detect the expression of SATB1 mRNA and protein in MDA-MB-435S、AGS、SGC-7901 and GES-1 cell line. Construction the eukaryotic expression vector pcDNA3.0-SATB1 and DNA double restriction enzyme digestion identification of plasmid. After transient transfection of SGC-7901 cells 48 h, RT-PCR and Western blot detection the expression of SATB1 mRNA and protein; MTT assay detection the cell proliferation; Flow cytometry analysis of cell-cycle arrest and apoptosis; transwell chamber assay detection the cell invasion; RT-PCR and Western blot detection the expression of heparanase. Design and synthesis of SATB1 siRNA oligonucleotides, After transient transfection of AGS cells 48 h, RT-PCR and Western blot detection the expression of SATB1 mRNA and protein; MTT assay detection the cell proliferation; Flow cytometry analysis of cell-cycle arrest and apoptosis; transwell chamber assay detection the cell invasion; RT-PCR and Western blot detection the expression of heparanase.
Results:Immunohistochemical analysis of 48 gastric cancer samples showed that 41 samples were positively expressed and the positive rate was 85.42%(41/48), however, the positive rate was only 4.17%(2/48) in adjacent tissues. RT-PCR showed in cancer samples and adjacent tissues the positive expression of SATB1 mRNA were 87.50%(42/48) and 25 %(3/48), respectively (p<0.01). The SATB1/β-actin mRNA rate in MDA-MB-435S, AGS, SGC-7901 and GES-1 cell lines were 0.437±0.021; 0.269±0.017; 0.019±0.006 and 0.011±0.003, respectively. Western Blot showed that the expression of SATB1 protein in AGS cell was higher than that in SGC-7901 cell (p<0.01). After transient transfection of SGC-7901 cells 48 h, RT-PCR showed that the SATB1/β-actin mRNA was 0.537±0.028 in pcDNA3.0-SATB1 transfection group and 0.098±0.007 in blank control group(p<0.05). Western Blot showed the SATB1/β-actin protein was 0.196±0.013 in pcDNA3.0-SATB1 transfection group and 0.067±0.008 in blank control group (p<0.05). MTT assay showed the proliferation ability of the SGC-7901 cell line in pcDNA3.0-SATB1 transfection group was enhanced (p<0.05).Flow cytometry showed that cycle distribution (G0/G1, S, G2/M) of blank control group, pcDNA3.0 transfection group and pcDNA3.0-SATB1 transfection group were G0/G1:65.27±5.38,78.36±4.64,52.28±4.13; S:24.52±1.68,10.25±1.13, 27.95±0.31, G2/M:10.21±1.13,11.39±0.96,19.77±1.02, respectively; the rate of G2/M in pcDNA3.0-SATB1 group increased (p<0.05). The apoptosis rates of three group were similar (p>0.05). Transwell chamber assay showed that the cell in blank control group, pcDNA3.0 transfection group and pcDNA3.0-SATBl transfection group were 47.26±3.39, 44.65±3.11 and 128.67±9.13, respectively. The cell number in pcDNA3.0-SATB1 transfection group was higher than those of other two group (p<0.05). RT-PCR and Western Blot showed that the expression of heparanase was unregulated in pcDNA3.0-SATB1 transfection group (p<0.05). aiRNA transfection could effectively silence gene expression. When AGS cell was transfected with SATB1-siRNA or SATB1-aiRNA, the expression of SATB1 was down-regulated in both group compared with control group (p<0.05), and SATB1-aiRNA could more effectively silence SATB1 mRNA expression (p<0.05). MTT assay showed the proliferation of the AGS cell line in SATBl-siRNA and SATB1-aiRNA transfection group was inhibited (p<0.05). Flow cytometry showed that percentage of G0/G1 was increased in SATBl-siRNA and SATBl-aiRNA transfection group (p<0.05), indicating of G0/G1 arrest. The apoptosis rate in control, SATB1-siRNA and SATBl-aiRNA transfection group was 2.69±0.09,6.37±0.42,10.12±0.61, respectively (p<0.05). Transwell chamber assay showed that the cells in control group, SATB1-siRNA and SATB1-aiRNA transfection group were 137.67±12.36,73.54±10.61 and 31.55±4.27, respectively (p<0.05). RT-PCR and Western Blot showed that the expression of heparanase were both down-regulated in SATB1-siRNA and SATB1-aiRNA transfection group (p<0.05).
Conclusion:The SATB1 gene was high positive expression in gastric cancer, and the expression of SATB1 is higher in AGS cell line than in SGC-7901 cell line. Up-regulation the expression of SATB1 in SGC-7901 cell could induce the cell proliferation, accelerate cell cycle progression, enhance invasive potential, and increase the expression of heparanase; however, down-regulation the expression of SATB1 in AGS cell could inhibit the cell proliferation, induce G0/G1 cell cycle arrest and cell apoptosis, reduce invasive potential and decrease the expression of heparanase. SATB1 could be involved in the progression of gastric cancer. It may be a new important prognostic indicators and therapeutic target of gastric cancer.
引文
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