下调整合素连接激酶对宫颈癌细胞糖酵解及增殖、凋亡的影响

史娟; 樊霞

doi:10.16016/j.1000-5404.201804008

您当前的位置：

首页 >

文章列表页 >

下调整合素连接激酶对宫颈癌细胞糖酵解及增殖、凋亡的影响

基础医学 | 更新时间：2026-01-09

- 下调整合素连接激酶对宫颈癌细胞糖酵解及增殖、凋亡的影响
- Down-regulation of integrin-linked kinase suppresses glycolysis and proliferation and promotes apoptosis of cervical cancer cells possibly by inhibiting Wnt/β-catenin pathway
- 第三军医大学学报 2018年40卷第18期页码：1668-1673
- 作者机构：
  
  1.716000 陕西延安，延安大学医学院:外妇护理教研室
  2.716000 陕西延安，延安大学医学院:预防医学教研室
- 作者简介：
  
  [ 樊霞，E-mail:fxyz-666@163.com FAN Xia, E-mail: fxyz-666@163.com
- 基金信息：
- DOI：10.16016/j.1000-5404.201804008
  中图分类号： R73-36; R730.51; R737.33
- 收稿：2018-04-02，
  
  修回：2018-06-05，
  
  纸质出版：2018-09-30
- 稿件说明：
移动端阅览
史娟, 樊霞. 下调整合素连接激酶对宫颈癌细胞糖酵解及增殖、凋亡的影响[J]. 第三军医大学学报, 2018,40(18):1668-1673.

Juan SHI, Xia FAN. Down-regulation of integrin-linked kinase suppresses glycolysis and proliferation and promotes apoptosis of cervical cancer cells possibly by inhibiting Wnt/β-catenin pathway[J]. Journal of Third Military Medical University, 2018, 40(18): 1668-1673.
史娟, 樊霞. 下调整合素连接激酶对宫颈癌细胞糖酵解及增殖、凋亡的影响[J]. 第三军医大学学报, 2018,40(18):1668-1673. DOI： 10.16016/j.1000-5404.201804008.

Juan SHI, Xia FAN. Down-regulation of integrin-linked kinase suppresses glycolysis and proliferation and promotes apoptosis of cervical cancer cells possibly by inhibiting Wnt/β-catenin pathway[J]. Journal of Third Military Medical University, 2018, 40(18): 1668-1673. DOI： 10.16016/j.1000-5404.201804008.

摘要

目的

观察下调整合素连接激酶(integrin-linked kinase，ILK)对宫颈癌细胞糖酵解及增殖、凋亡的影响，探讨其相关作用机制。

方法

选择宫颈癌细胞CaSki，细胞分3组，转染ILK siRNA、siRNA control分别为干扰组和阴性组，以未转染的细胞为对照组。qRT-PCR、Western blot检测细胞中ILK mRNA、蛋白表达水平。试剂盒检测细胞中丙酮酸激酶(pyruvate kinase，PK)、己糖激酶(hexokinase，HK)、三磷腺苷(adenosine triphosphate，ATP)水平和培养液中乳酸水平，MTT法检测细胞增殖，流式细胞术检测细胞凋亡，Western blot检测细胞中活化的含半胱氨酸的天冬氨酸蛋白水解酶3(cleaved Caspase-3)、活化的含半胱氨酸的天冬氨酸蛋白水解酶9(cleaved Caspase-9)、β-连环蛋白(β-catenin)、c-myc蛋白水平。

结果

ILK siRNA能够下调宫颈癌细胞中ILK mRNA和蛋白水平，siRNA control对细胞中ILK mRNA和蛋白水平没有影响。阴性组PK、HK、ATP、乳酸水平、细胞存活率、凋亡率、cleaved Caspase-3、cleaved Caspase-9、β-catenin、c-myc表达水平与对照组相比差异均无统计学意义(

0.05)。与对照组比较，干扰组PK、HK、ATP、乳酸水平明显降低，细胞存活率明显降低，细胞凋亡率明显升高，细胞中cleaved Caspase-3、cleaved Caspase-9表达水平升高，β-catenin、c-myc表达水平下降，差异均有统计学意义(

0.05)。

结论

下调ILK抑制宫颈癌细胞糖酵解和细胞增殖，促进细胞凋亡，作用机制可能与下调Wnt/β-catenin信号通路的激活有关。

Abstract

Objective

To study the effect of small interfering RNA (siRNA)-mediated down-regulation of integrin-linked kinase (ILK) on glycolysis

proliferation

and apoptosis of cervical cancer cells and explore the underlying mechanism.

Methods

Human cervical cancer CaSki cells were transfected with a specific siRNA targeting ILK and a control siRNA

and the changes in the expression levels of ILK mRNA and protein were detected using qRT-PCR and Western blotting. The levels of pyruvate kinase (PK)

hexokinase (HK)

ATP and lactic acid in the culture medium were detected using a commercial detection kits. The changes in the proliferation and apoptosis of the transfected cells were detected using MTT assay and flow cytometry

respectively

and the expression levels of cleaved Caspase-3

cleaved Caspase-9

β-catenin and c-myc proteins were detected using Western blotting.

Results

Transfection with ILK siRNA

but not the control siRNA

significantly reduced ILK mRNA and protein expressions in the cells. Transfection of the cells with ILK siRNA caused significant reduction in the levels of PK

ATP and lactic acid in the culture medium

significantly decreased cell survival rate

increased apoptosis rate

enhanced the levels of cleaved Caspase-3 and Cleaved caspase-9

and lowered the expressions of β-catenin and c-myc as compared with the control cells (

0.05).

Conclusion

Down-regulation of ILK inhibits glycolysis and cell growth and promotes cell apoptosis of cervical cancer cells in vitro possibly by inhibiting the activation of Wnt/β-catenin signaling pathway.

关键词

Keywords

references

LIU S, SONG L, ZENG S, et al . MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells[J ] . Tumour Biol, 2016, 37(1): 633-640. DOI: 10.1007/s13277-015-3732-4.

HART P C, RATTI B A, MAO M, et al . Caveolin-1 reg ulates cancer cell metabolism via scavenging Nrf2 and suppressing MnSOD-driven glycolysis[J ] . Oncotarget, 2016, 7(1): 308-322. DOI: 10.18632/oncotarget.5687..

GARCíA-JéREZ A, LUENGO A, CARRACEDO J, et al . Effect of uraemia on endothelial cell damage is mediated by the integrin linked kinase pathway[J ] . J Physiol, 2015, 593(3): 601-618. DOI: 10.1113/jphysiol.2014.283887.

李胜水, 张凤梅, 李秀清, 等. ILK和E-Cad蛋白表达与食管鳞癌浸润转移的关系[J].现代肿瘤医学, 2015, 23(6): 808-811. DOI: 10.3969/j.issn.1672-4992.2015.06.23.

LI S S, ZHANG F M, LI X Q, et al . ILK and E-Cad expression and their relation to invasion and metastases in human esophageal squamous cell carcinoma[J ] . J Mod Oncol, 2015, 23 (6): 808-811. DOI: 10.3969/j.issn.1672- 4992.2015.06.23.

朱向阳, 王香花.ILK在宫颈癌组织中的表达及宫颈癌细胞侵袭能力的影响[J].中国妇幼健康研究, 2016, 27(1): 87-89. DOI: 10.3969/j.issn.1673-5293.2016.01.030.

ZHU X Y, WANG X H. Expression of ILK in cervical cancer tissues and its influence on cervical cancer cell invasion[J]. Chin Matern Child Health Res, 2016, 27 (1): 87-89. DOI: 10.3969/j.issn.1673- 5293.2016.01.030.

HAUSMANN C, TEMME A, CORDES N, et al . ILKAP, ILK and PINCH1 control cell survival of p53-wildtype glioblastoma cells after irradiation[J ] . Oncotarget, 2015, 6(33): 34592-34605. DOI: 10.18632/oncotarget.5423.

AKHTAR N, STREULI C H. An integrin-ILK-microtubule network orients cell polarity and lumen formation in glandular epithelium[J]. Nat Cell Biol, 2013, 15(1): 17-27. DOI: 10.1038/ncb2646.

MATSUI Y, ASSI K, OGAWA O, et al . The importance of integrin-linked kinase in the regulation of bladder cancer invasion[J ] . Int J Cancer, 2012, 130(3): 521-531. DOI: 10. 1002/ijc.26008.

XING Y, QI J, DENG S, et al . Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition[J ] . Exp Cell Res, 2013, 319(13): 2058-2072. DOI: 10.1016/j.yexcr.2013.05.014.

LIANG F, WANG B, BAO L, et al . Overexpression of ILK promotes temozolomide resistance in glioma cells[J ] . Mol Med Rep, 2017, 15(3): 1297-1304. DOI: 10. 3892/mmr.2017.6157.

SRIVASTAVA S K, BHARDWAJ A, ARORA S, et al . MicroRNA-345 induces apoptosis in pancreatic cancer cells through potentiation of caspase-dependent and -ind ependent pathways[J ] . Br J Cancer, 2015, 113(4): 660-668. DOI: 10.1038/bjc.2015.252.

CUI R, KIM T, FASSAN M, et al . MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7[J ] . Oncotarget, 2015, 6(26): 21802-21815. DOI: 10.18632/oncotarget.5224.

LIU C, VOJNOVIC D, KOCHEVAR I E, et al . UV-A irradiation activates Nrf2-regulated antioxidant defense and induces p53/Caspase3-dependent apoptosis in corneal endothelial cells[J ] . Invest Ophthalmol Vis Sci, 2016, 57(4): 2319-2327. DOI: 10.1167/iovs.16-19097.

TIAN H, ZHANG D F, ZHANG B F, et al . Melanoma differentiation associated gene-7/interleukin-24 induces Caspase-3 denitrosylation to facilitate the activation of cancer cell apoptosis[J ] . J Interferon Cytokine Res, 2015, 35(3): 157-167. DOI: 10.1089/jir.2014.0061.

DAS D, PERSAUD L, DEJOIE J, et al . Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates caspases in human prostate cancer cells through sigma 1 receptor[J ] . Biochem Biophys Res Commun, 2016, 470(2): 319-323. DOI: 10.1016/j.bbrc.2016.01.055.

KANG N, CAO S J, ZHOU Y, et al . Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells[J ] . Int J Oncol, 2015, 47(6): 2045-2056. DOI: 10.3892/ijo.2015.3186.

BRENTNALL M, RODRIGUEZ-MENOCAL L, DE GUEVARA R L, et al . Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis[J ] . BMC Cell Biol, 2013, 14(1): 32. DOI: 10.1186/1471- 2121-14-32.

LIU G, LI Y I, GAO X. Overexpression of microRNA-133b sensitizes non-small cell lung cancer cells to irradiation through the inhibition of glycolysis[J]. Oncol Lett, 2016, 11(4): 2903-2908. DOI: 10. 3892/ol.2016.4316.

DRUZHKOVA I N, SHIRMANOVA M V, LUKINA M M, et al . The metabolic interaction of cancer cells and fibroblasts - coupling between NAD(P)H and FAD, intracellular pH and hydrogen peroxide[J ] . Cell Cycle, 2016, 15(9): 1257-1266. DOI: 10.1080/15384101.2016. 1160974.

LUO F, LIU X, LING M, et al . The lncRNA MALAT1, acting through HIF-1α stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells[J ] . Biochim Biophys Acta, 2016, 1862(9): 1685-1695. DOI: 10. 1016/j.bbadis.2016.06.004.

LI H, JIAO S, LI X, et al . Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling[J ] . Biochem Biophys Res Commun, 2015, 467(1): 14-20. DOI: 10.1016/j.bbrc.2015.09.140.

郑昆明, 吴刚, 秦晓明, 等. XAV939对肝癌细胞增殖及糖酵解的影响[J].现代肿瘤医学, 2016, 24(13): 2023-2026. DOI: 10.3969/j.issn.1672-4992.2016.13.004.

ZHENG K M, WU G, QIN X M, et al . Effects of XAV939 on proliferation and glycolysis of hepatocellular carcinoma cells[J ] . J Mod Oncol, 2016, 24 (13): 2023-2026. DOI: 10. 3969/j.issn.1672-4992.2016.13.004.

PATE K T, STRINGARI C, SPROWL-TANIO S, et al . Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer[J ] . EMBO J, 2014, 33(13): 1454-1473. DOI: 10.15252/embj.201488598.

PIAO Z, HONG C S, JUNG M R, et al . Thymosin β4 induces invasion and migration of human colorectal cancer cells through the ILK/AKT/β-catenin signaling pathway[J ] . Biochem Biophys Res Commun, 2014, 452(3): 858-864. DOI: 10.1016/j.bbrc.2014.09.012.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

多沙唑嗪通过转录因子激活蛋白-2α诱导HeLa细胞凋亡

MiR-616在骨肉瘤中的表达及对其细胞增殖、凋亡、迁移侵袭的作用

Gm49394对胰岛β细胞凋亡的调控及机制研究

全身炎症反应指数联合临床病理参数预测宫颈癌复发的模型建立与验证

Kallistatin诱导SIRT1表达抑制人髓核细胞凋亡及细胞外基质降解