VEGF-B在人绒毛膜癌侵袭转移中作用的研究
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摘要
【目的】
(1)检测血管内皮生长因子-B(vascular endothelial growthfactor-B,VEGF-B)在人绒毛膜癌不同侵袭力细胞JEG-3和JAR内表达,探讨VEGF-B高表达与绒毛膜癌侵袭转移的关系;(2)了解RNA干扰沉默VEGF-B基因对绒毛膜癌高侵袭力JEG-3细胞侵袭力的抑制作用。
【方法】
(1)运用半定量逆转录一聚合酶链反应(reverse transcriptase—polymerase chain reaction,RT-PCR)检测绒毛膜癌细胞JEG-3和JAR中VEGF-B mRNA的表达情况,Matrigel体外侵袭实验检测两种细胞侵袭能力,并比较差异;②构建VEGF-B特异shRNA(short hairpinRNA,小发夹RNA),并转染入高侵袭力JEG-3细胞;③检测转染前后VEGF-B mRNA表达的差异,并比较该细胞体外侵袭力的变化。
【结果】
(1)在两种细胞中均检测到VEGF-B mRNA表达,相对低侵袭性JAR细胞,高侵袭性JEG-3细胞中VEGF-B mRNA表达明显增加(P＜0.05),相关性分析显示VEGF-B mRNA的表达水平与绒毛膜癌细胞侵袭力呈正相关(r=0.782,P＜0.05);(2)转染后JEG-3细胞内VEGF-B mRNA的表达下降(P＜0.05);(3)与阴性对照组、空白组相比,转染后JEG-3细胞的体外侵袭力亦下降(P＜0.05)。
【结论】
(1)VEGF-B参与绒毛膜癌的发生和发展,除了跟VEGF家族其他成员一样,促进肿瘤血管新生外,还与绒毛膜癌的侵袭和转移有关;(2)VEGF-B shRNA的成功转染,有效抑制了目的基因VEGF-B在JEG-3细胞中的表达;(3)抑制VEGF-B mRNA的表达,可以减低JEG-3细胞的侵袭力。
Objective
(1) To investigate the association between the expression of VEGF-B (vascular endothelial growth factor-B) and the invasion and metastasis of choriocarcinoma. (2) To explore the effect of VEGF-B short hairpin RNA(shRNA) on the invasion of chaoriocarcinoma cell line-JEG-3.
Methods
(1) Expression of VEGF-B gene in the human choriocarcinoma cell lines (JEG-3 cells and JAR cells) were detected by semi-quantitative RT-PCR(reverse transcriptase-polymerase chain reaction).(2) Construct short hairpin RNA of VEGF-B, transfect it to JEG-3 cells. (3)The effect of VEGF-B shRNA transfection on the expression of VEGF-B mRNA and the invasion of JEG-3 cells were measured by RT-PCR and Matrigel invasion assay.
Results
(1)The expression of VEGF-B gene in JEG-3 cells were significantly stronger than that in JAR cells (P<0.05) .The invasion ability of JEG-3 cell line was stronger than that of JAR cell line (P< 0.05) .There was significantly positive correlation between VEGF-B and the invasiveness of choriocarcinoma cells(r=0.782, P<0.05).(2)After transfection,the expression of VEGF mRNA in JEG-3 cells decreased (P <0.05) .(3) After transfection, the invasion of JEG-3 cells also went down (P<0.05) .
Conclusion
(1)The existence of VEGF-B gene in JEG-3 and JAR cell lines may be play an important role in the metastasis and invasion of human choriocarcinoma,except promoting angiogenesis like other members of VEGF.(2)VEGF-B shRNA can inhibit the expression of VEGF-B gene in JEG-3 cells. (3)VEGF-B shRNA can inhibit the invasion of JEG-3 cells.
(1)检测血管内皮生长因子-B(vascular endothelial growthfactor-B,VEGF-B)在人绒毛膜癌不同侵袭力细胞JEG-3和JAR内表达,探讨VEGF-B高表达与绒毛膜癌侵袭转移的关系;(2)了解RNA干扰沉默VEGF-B基因对绒毛膜癌高侵袭力JEG-3细胞侵袭力的抑制作用。
【方法】
(1)运用半定量逆转录一聚合酶链反应(reverse transcriptase—polymerase chain reaction,RT-PCR)检测绒毛膜癌细胞JEG-3和JAR中VEGF-B mRNA的表达情况,Matrigel体外侵袭实验检测两种细胞侵袭能力,并比较差异;②构建VEGF-B特异shRNA(short hairpinRNA,小发夹RNA),并转染入高侵袭力JEG-3细胞;③检测转染前后VEGF-B mRNA表达的差异,并比较该细胞体外侵袭力的变化。
【结果】
(1)在两种细胞中均检测到VEGF-B mRNA表达,相对低侵袭性JAR细胞,高侵袭性JEG-3细胞中VEGF-B mRNA表达明显增加(P＜0.05),相关性分析显示VEGF-B mRNA的表达水平与绒毛膜癌细胞侵袭力呈正相关(r=0.782,P＜0.05);(2)转染后JEG-3细胞内VEGF-B mRNA的表达下降(P＜0.05);(3)与阴性对照组、空白组相比,转染后JEG-3细胞的体外侵袭力亦下降(P＜0.05)。
【结论】
(1)VEGF-B参与绒毛膜癌的发生和发展,除了跟VEGF家族其他成员一样,促进肿瘤血管新生外,还与绒毛膜癌的侵袭和转移有关;(2)VEGF-B shRNA的成功转染,有效抑制了目的基因VEGF-B在JEG-3细胞中的表达;(3)抑制VEGF-B mRNA的表达,可以减低JEG-3细胞的侵袭力。
Objective
(1) To investigate the association between the expression of VEGF-B (vascular endothelial growth factor-B) and the invasion and metastasis of choriocarcinoma. (2) To explore the effect of VEGF-B short hairpin RNA(shRNA) on the invasion of chaoriocarcinoma cell line-JEG-3.
Methods
(1) Expression of VEGF-B gene in the human choriocarcinoma cell lines (JEG-3 cells and JAR cells) were detected by semi-quantitative RT-PCR(reverse transcriptase-polymerase chain reaction).(2) Construct short hairpin RNA of VEGF-B, transfect it to JEG-3 cells. (3)The effect of VEGF-B shRNA transfection on the expression of VEGF-B mRNA and the invasion of JEG-3 cells were measured by RT-PCR and Matrigel invasion assay.
Results
(1)The expression of VEGF-B gene in JEG-3 cells were significantly stronger than that in JAR cells (P<0.05) .The invasion ability of JEG-3 cell line was stronger than that of JAR cell line (P< 0.05) .There was significantly positive correlation between VEGF-B and the invasiveness of choriocarcinoma cells(r=0.782, P<0.05).(2)After transfection,the expression of VEGF mRNA in JEG-3 cells decreased (P <0.05) .(3) After transfection, the invasion of JEG-3 cells also went down (P<0.05) .
Conclusion
(1)The existence of VEGF-B gene in JEG-3 and JAR cell lines may be play an important role in the metastasis and invasion of human choriocarcinoma,except promoting angiogenesis like other members of VEGF.(2)VEGF-B shRNA can inhibit the expression of VEGF-B gene in JEG-3 cells. (3)VEGF-B shRNA can inhibit the invasion of JEG-3 cells.
引文
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[2]Paavonen K,Horelli-Kuitumen N,Chilov D,et al.Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localized to chromosomes 11q13 and 4q34,respectively[J].Circulation,1996,93(6):1079.
[3]Olofsson B,Pajusola K,Kaipainen A,et al.Vaascular endothelial growth factor B,a novel growth factor for endothelial cells[J].Pro Natl Acad Sci USA,1996,93(6):2576.
[4]Lahteenvuo JE,Lahteenvuo MT,Kivela A,et al.Vascular endothelial growth factor-B induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1 and neuropilin receptor-1dependent mechanisms[J].Circulation.2009 Feb 17;119(6):845-56.
[5]Silvestre JS,Tamarat R,Ebrahimian TG,et al.Vascular endothelial growth factor-B promotes in vivo angiogenesis[J].Circ Res.2003 Jul 25;93(2):114-23.Epub 2003 Jun 12.
[6]Mylona E,Alexandrou P,Giannopoulou I,et al.The prognostic value of vascular endothelial growth factors(VEGFs)-A and -B and their receptor,VEGFR-1,in invasive breast carcinoma[J].Gynecol Oncol.2007 Mar;104(3):557-63.Epub 2006 Dec 5.
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