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河北医科大学 第一医院,石家庄 050000
李亚威,硕士,副主任技师,从事妇科肿瘤临床检验与诊断学研究,E-mail:lywydyy@163.com
王娜,硕士,主治医师,从事妇科肿瘤的诊断及治疗研究,E-mail:wangna5421@126.com
收稿日期:2021-10-09,
网络出版日期:2021-11-26,
纸质出版日期:2022-02-20
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李亚威,谢磊,王娜.毛钩藤碱对人宫颈癌Ca Ski细胞增殖、凋亡、转移及侵袭的影响[J].中国实验方剂学杂志,2022,28(04):109-115.
LI Ya-wei,XIE Lei,WANG Na.Effect of Hirsutine on Proliferation, Apoptosis, Metastasis, and Invasion of Human Cervical Cancer Ca Ski Cells[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(04):109-115.
李亚威,谢磊,王娜.毛钩藤碱对人宫颈癌Ca Ski细胞增殖、凋亡、转移及侵袭的影响[J].中国实验方剂学杂志,2022,28(04):109-115. DOI: 10.13422/j.cnki.syfjx.20220323.
LI Ya-wei,XIE Lei,WANG Na.Effect of Hirsutine on Proliferation, Apoptosis, Metastasis, and Invasion of Human Cervical Cancer Ca Ski Cells[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(04):109-115. DOI: 10.13422/j.cnki.syfjx.20220323.
目的
2
探讨毛钩藤碱对人宫颈癌Ca Ski细胞增殖、凋亡、转移、侵袭的影响及机制。
方法
2
细胞活性与增殖检测(CCK-8)法检测细胞增殖活性,Hoechst 33258染色及流式细胞术检测细胞凋亡,实时荧光定量聚合酶链式反应检测B细胞淋巴瘤-2(Bcl-2),Bcl-2相关X蛋白(Bax),p53 mRNA表达,划痕实验检测细胞转移能力,Transwell小室实验检测细胞侵袭能力,酶联免疫吸附测定(ELISA)检测纤连蛋白(FN),基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-9(MMP-9)含量,蛋白免疫印迹法(Western blot)检测蛋白表达。
结果
2
与空白组比较,毛钩藤碱可以呈剂量及时间依赖性的抑制Ca Ski细胞的增殖;8.0,16.0,32.0 μmol·L
-1
毛钩藤碱组细胞凋亡率,Bax,p53 mRNA表达增加(
P
<
0.05,
P
<
0.01),Bcl-2 mRNA及磷酸化Src(p-Src),磷酸化信号转导和转录活化因子3(p-STAT3)蛋白表达降低(
P
<
0.05,
P
<
0.01)。与空白组比较,1.0,2.0,4.0 μmol·L
-1
毛钩藤碱组细胞迁移率,穿膜细胞数,FN,MMP-2,MMP-9含量及缺氧诱导因子-1
α
(HIF-1
α
),波形蛋白(Vimentin),N-钙黏蛋白(N-cadherin)表达降低(
P
<
0.05,
P
<
0.01),E-钙黏蛋白(E-cadherin)表达增加(
P
<
0.01)。
结论
2
毛钩藤碱可以抑制人宫颈癌Ca Ski细胞的增殖、转移及侵袭,并能诱导凋亡,作用机制与调控Src/STAT3及HIF-1
α
/上皮间充质转化(EMT)信号通路有关。
Objective
2
To investigate the effects of hirsutine on proliferation, apoptosis, metastasis, and invasion of human cervical cancer Ca Ski cells and its action mechanism.
Method
2
The cell proliferation was determined by cell counting kit-8 (CCK-8) assay and the cell apoptosis by Hoechst 33258 staining and flow cytometry. The mRNA expression levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and p53 were detected by real-time fluorescence quantitative polymerase chain reaction. The scratch test was conducted to detect the cell mobility, followed by the detection of cell invasion ability using a Transwell chamber. The contents of fibronectin (FN), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were measured by enzyme linked immunosorbent assay (ELISA), and their protein expression levels were assayed by Western blot.
Result
2
Compared with the control group, hirsutine inhibited the proliferation of Ca Ski cells in a dose- and time-dependent manner. The apoptosis rates and Bax and p53 mRNA expression levels in the 8.0, 16.0, 32.0 μmol·L
-1
hirsutine groups rose (
P
<
0.05,
P
<
0.01), while the Bcl-2 mRNA expression and phosphorylated Src (p-Src) and phosphorylated signal transducer and activator of transcription factor 3 (STAT3) protein expression declined (
P
<
0.05,
P
<
0.01). Compared with the control group, the 1.0, 2.0, 4.0 μmol·L
-1
hirsutine groups exhibited lowered cell mobility, number of transmembrane cells, FN, MMP-2 and MMP-9 contents, and hypoxia inducible factor-1
α
(HIF-1
α
), Vimentin, and N-cadherin protein expression (
P
<
0.05,
P
<
0.01), but elevated E-cadherin protein expression (
P
<
0.01).
Conclusion
2
Hirsutine inhibits the proliferation, metastasis, and invasion of human cervical cancer Ca Ski cells and induces their apoptosis, which may be related to its regulation of Src/STAT3 and HIF-1
α
/epithelial mesenchymal transformation (EMT) signaling pathways.
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