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敲低核转运蛋白对人骨肉瘤细胞增殖和血管生成的体内影响
Karyopherina 2 knockdown inhibits osteosarcoma cell proliferation and angiogenesis in mice by suppressing Sox2 expression
- 第三军医大学学报 2019年41卷第14期 页码：1308-1313
- 作者机构：
030000 太原，山西医科大学第二临床医学院骨科
- 作者简介：
[吕智，E-mail:zhilv2013@163.comLYU Zhi, E-mail:zhilv2013@163.com
- 基金信息：国家自然科学基金面上项目(81772867);山西省自然科学基金(2015011097)
DOI：10.16016/j.1000-5404.201901004
中图分类号： R394.3; R730.23; R738.1收稿：2019-01-01，
修回：2019-03-20，
纸质出版：2019-07-30
- 稿件说明：
移动端阅览
葛乔枫, 张龙, 孙晓娟, 等. 敲低核转运蛋白对人骨肉瘤细胞增殖和血管生成的体内影响[J]. 第三军医大学学报, 2019,41(14):1308-1313.
Qiaofeng GE, Long ZHANG, Xiaojuan SUN, et al. Karyopherina 2 knockdown inhibits osteosarcoma cell proliferation and angiogenesis in mice by suppressing Sox2 expression[J]. Journal of Third Military Medical University, 2019, 41(14): 1308-1313.
葛乔枫, 张龙, 孙晓娟, 等. 敲低核转运蛋白对人骨肉瘤细胞增殖和血管生成的体内影响[J]. 第三军医大学学报, 2019,41(14):1308-1313. DOI： 10.16016/j.1000-5404.201901004.
Qiaofeng GE, Long ZHANG, Xiaojuan SUN, et al. Karyopherina 2 knockdown inhibits osteosarcoma cell proliferation and angiogenesis in mice by suppressing Sox2 expression[J]. Journal of Third Military Medical University, 2019, 41(14): 1308-1313. DOI： 10.16016/j.1000-5404.201901004.
摘要
目的
2
探讨核转运蛋白2(karyopherina 2，KPNA2)对人骨肉瘤(osteosarcoma，OS)细胞增殖和血管生成的影响，并从分子层面分析其可能的作用机制。
方法
2
构建Sh-KPNA2慢病毒载体(Sh-KPNA2组)及空载体Sh-Control(Sh-Control组)转染骨肉瘤细胞Saos-2，观察敲低KPNA2后对Saos-2细胞增殖的影响；利用转染Sh-KPNA2和空载体Sh-Control的Saos-2细胞分别构建OS动物模型，小动物活体荧光分子断层成像系统(fluorescence molecular tomography，FMT)验证KPNA2对瘤体血管生成的影响；qRT-PCR和Western blot验证瘤体内KPNA2和睾丸决定因子Y染色体性别决定区基因(SRY related HMG box-2，Sox2)的mRNA和蛋白表达水平。
结果
2
Sh-KPNA2组细胞增殖能力较Sh-Control组明显降低(
P
＜0.05)；Sh-KPNA2组荷瘤小鼠瘤体积显著小于Sh-Control组(
P
＜0.05)；免疫组化和FMT扫描结果显示，Sh-Control组的血管生成能力显著高于Sh-KPNA2组(
P
＜0.05)；瘤体qRT-PCR和Western blot检测结果均显示Sox2在Sh-Control组中表达显著高于Sh-KPNA2组(
P
＜0.05)。
结论
2
敲低KPNA2可抑制OS增殖和血管生成，其机制可能与KPNA2影响Sox2的表达有关。
Abstract
Objective
2
To explore the effect of karyopherina 2 (KPNA2) knockdown on osteosarcoma cell proliferation and angiogenesis and the possible molecular mechanism.
Methods
2
We transfected Saos-2 cells with a Sh-KPNA2 lentiviral vector or a control vector (Sh-Control) to observe the effect of KPNA2 knockdown on the cell proliferation. We further observed tumor angiogenesis in nude mice bearing xenografts derived from Saos-2 cells transfected with Sh-KPNA2 or Sh-Control vector using a fluorescence molecular tomography (FMT) system. qRT-PCR and Western blotting were performed to detect the mRNA and protein expression of KPNA2 and SRY-related HMG box-2 (Sox2) in the xenografts.
Results
2
Saos-2 cells transfected with Sh-KPNA2 vector showed significantly lowered proliferation capacity as compared with the cells transfected with Sh-Control vector (
P
<
0.05). In the tumor-bearing nude mice
the tumor volume and weight were both significantly lower in Sh-KPNA2 group than in Sh-Control group (
P
<
0.05). The results of FMT scan and immunohistochemistry both showed weakened angiogenesis in the xenografts in Sh-KPNA2 group in comparison with Sh-Control group (
P
<
0.05). Sox2 expression at both the mRNA and protein levels in the xenografts was significantly lower in Sh-KPNA2 group than in Sh-Control group (
P
<
0.05).
Conclusion
2
KPNA2 knockdown inhibits the proliferation and angiogenesis of osteosarcoma cells possibly as a result of lowered expression of Sox2.
关键词
Keywords
references
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