Kif2a沉默对人上皮卵巢癌细胞增殖、侵袭及凋亡的影响-现代医学

Kif2a沉默对人上皮卵巢癌细胞增殖、侵袭及凋亡的影响

单位：1. 第四军医大学唐都医院肿瘤科, 陕西西安 710038;
2. 泾阳县医院内科, 陕西咸阳 713700

分类号：R737.31

出版年·卷·期（页码）：2017·36·第四期（546-551）

摘要：

目的：探讨Kif2a在人上皮卵巢癌细胞中的表达及其沉默对癌细胞增殖、侵袭及凋亡的影响。方法：选取人上皮卵巢癌细胞株（OVCAR-3，SKOV-3）及人正常卵巢上皮细胞株（IOSE-80）进行常规培养；采用荧光定量PCR （q-PCR）和Western blot法检测各细胞中Kif2a基因及蛋白的表达量；以siRNA干扰法对癌细胞中的Kif2a基因进行沉默，沉默效果以q-PCR及Western blot法验证；MTT法检测细胞增殖；Transwell实验检测细胞侵袭能力；细胞凋亡率以流式细胞术进行检测；凋亡相关蛋白active-caspase 3及Bcl-2表达以Western blot法检测。结果：Kif2a在人上皮卵巢癌细胞中的表达均显著高于人正常卵巢上皮细胞。Kif2a基因沉默后，OVCAR-3和SKOV-3细胞增殖及侵袭能力均显著下降；细胞凋亡率显著增加，并伴随促凋亡蛋白active-caspase 3表达显著上升及抑凋亡蛋白Bcl-2表达显著下降。结论：Kif2a在人上皮卵巢癌细胞中表达显著上升，其沉默能够抑制上皮卵巢癌细胞的增殖和侵袭，并诱导细胞凋亡。

Objective: To explore the expression of Kif2a in human epithelial ovarian cancer cells, and the influences of Kif2a gene silencing on cancer cell proliferation, invasion and apoptosis. Methods: Human epithelial ovarian cancer cell lines (OVCAR-3, SKOV-3) and human normal ovarian epithelial cell line (IOSE-80) were routinely cultured. The levels of Kif2a mRNA and protein in cells were detected by qRT-PCR and Western blots, respectively. Kif2a gene in OVCAR-3 and SKOV-3 cells was silenced by siRNA-interference, which was verified by qRT-PCR and Western blots. Cell proliferation was measured by MTT assay. Cell invasion ability was determined by Transwell assay. Flow cytometry was used to detect cell apotosis rate. The expression of apottosis-related proteins (active-caspase 3 and Bcl-2) were detected by Western blot.Results: The expression of Kif2a in cancer cells was significantly higher than that in normal cells. After silencing Kif2a gene, the proliferation and invasion abilities of OVCAR-3 and SKOV-3 cells were markedly decreased. Oppositely, cell apoptosis rate was dramatically increased with enhanced active-caspase 3 expressions and reduced Bcl-2 expressions.Conclusion: For epithelial ovarian cancer, the expression of Kif2a is aberrantly increased in cancer cells. Silencing of Kif2a gene can dramatically inhibit epithelial ovarian cancer cell proliferation and invasion, but induce cell apoptosis.

参考文献：

[1] SIEGEL R,MA J,ZOU Z,et al.Cancer statistics,2014[J].CA Cancer J Clin,2014,64(1):9-29.
[2] 纪晓宁,丰有吉.上皮性卵巢癌病因学研究进展[J].中国癌症杂志,2014,24(11):861-864.
[3] JANG C Y,WONG J,COPPINGER J A,et al.DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement[J].The Journal of cell biology,2008,181(2):255-267.
[4] WANG J,MA S,MA R,et al.KIF2A silencing inhibits the proliferation and migration of breast cancer cells and correlates with unfavorable prognosis in breast cancer[J].BMC Cancer,2014,14(1):461-469.
[5] WANG C Q,LI Y J,WEI Z M,et al.Stable gene-silence of Kif2a synergistic with 5-fluorouracil suppresses oral tongue squamous cell carcinoma growth in vitro and in vivo[J].Oral Surg Oral Med Oral Pathol Oral Radiol,2013,116(1):49-54.
[6] 任艳艳,徐沙沙,张丽,等.肺鳞癌组织Kif2a与MMP-2的表达及其相关性[J].齐鲁医学杂志,2016,31(3):285-293.
[7] WANG D,ZHU H,YE Q,et al.Prognostic Value of KIF2A and HER2-Neu Overexpression in Patients With Epithelial Ovarian Cancer[J].Medicine,2016,95(8):e2803-e2810.
[8] 马丁.上皮性卵巢癌组织起源与肿瘤发生新进展-"二元论" 学说[J].中国实用妇科与产科杂志,2014,30(1):8-11.
[9] 由庆军,杜依燃.微管解聚蛋白Kif2a参与脑胶质细胞瘤的发生和进展[J].中国实用医药,2013,8(31):24-25.
[10] 周浩,沈涛.微管解聚酶驱动蛋白家族成员KIF2A研究进展[J].生命科学,2014,26(8):866-873.
[11] 张欣.Kif2a基因沉默对脑胶质瘤细胞生物学行为的影响及机制研究[D].山东大学,2015.
[12] WANG C Q,QU X,ZHANG X Y,et al.Overexpression of Kif2a promotes the progression and metastasis of squamous cell carcinoma of the oral tongue[J].Oral Oncol,2010,46(1):65-69.
[13] 王建丽,马榕,曲迅,等.乳腺癌组织中Kif2a过表达在肿瘤进展和转移中的作用[J].中国病理生理杂志,2010,26(10):2003-2004.
[14] WANG K,LIN C,WANG C,et al.Silencing Kif2a induces apoptosis in squamous cell carcinoma of the oral tongue through inhibition of the PI3K/Akt signaling pathway[J].Mol Med Rep,2014,9(1):273-278.

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