[1]王 洁),何振兴),赵菊花),等.紫草素对皮肤鳞状细胞癌细胞生长及PI3K/AKT信号通路的影响[J].郑州大学学报(医学版),2019,(03):414-418.[doi:10.13705/j.issn.1671-6825.2018.10.090]
 WANG Jie),HE Zhenxing),ZHAO Juhua),et al.Effects of shikonin on growth of cutaneous squamous cell carcinoma cells and PI3K/AKT signaling pathway[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2019,(03):414-418.[doi:10.13705/j.issn.1671-6825.2018.10.090]
点击复制

紫草素对皮肤鳞状细胞癌细胞生长及PI3K/AKT信号通路的影响()
分享到:

《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2019年03期
页码:
414-418
栏目:
应用研究
出版日期:
2019-05-20

文章信息/Info

Title:
Effects of shikonin on growth of cutaneous squamous cell carcinoma cells and PI3K/AKT signaling pathway
作者:
王 洁12)何振兴3)赵菊花12)李 达2)李 燃2)杨 羽2)
1)西南医科大学附属医院皮肤科 四川泸州 646000 2)南充市中心医院皮肤科 四川南充 637000 3)南充市中心医院肝胆外科 四川南充 637000
Author(s):
WANG Jie12)HE Zhenxing3)ZHAO Juhua12)LI Da2)LI Ran2)YANG Yu2)
1)Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000 2)Department of Dermatology, Nanchong Central Hospital,Nanchong, Sichuan 637000 3)Department of Hepatobiliary Surgery, Nanchong Central Hospital, Nanchong, Sichuan 637000
关键词:
紫草素 皮肤鳞状细胞癌细胞 生长抑制 PI3K/AKT信号通路
Keywords:
shikonin cutaneous squamous cell carcinoma cell growth inhibition PI3K/AKT signaling pathway
分类号:
R739.5
DOI:
10.13705/j.issn.1671-6825.2018.10.090
摘要:
目的:探讨紫草素对人皮肤鳞状细胞癌A431细胞生长及PI3K/AKT信号通路的影响。方法:将A431细胞分为对照组、紫草素低剂量组(10 μmol/L)、紫草素中剂量组(20 μmol/L)和紫草素高剂量组(40 μmol/L)。采用CCK-8法检测细胞活力,PI单染法检测细胞周期,Annexin V-FITC/PI双染法检测细胞凋亡,qRT-PCR检测细胞中增殖细胞核抗原(PCNA)和Cyclin B1 mRNA表达水平,Western blot检测细胞中丝苏氨酸蛋白激酶(AKT)和磷酸化AKT(p-AKT)蛋白的表达水平。结果:紫草素组A431细胞活力降低,且呈时间和剂量依赖性(P<0.001)。紫草素组A431细胞被阻滞于S期和G2/M期(P<0.001),且细胞凋亡增加(P<0.001),细胞中PCNA和Cyclin B1 mRNA的表达降低(P<0.001),p-AKT表达降低(P<0.001)。结论:紫草素可能通过抑制PI3K/AKT信号通路,抑制皮肤鳞状细胞癌细胞的生长。
Abstract:
Aim:To investigate the inhibitory effects of shikonin on the growth of human cutaneous squamous cell carcinoma A431 cells and to explore its effects on PI3K/AKT signaling pathway.Methods:A431 cells were cultured in vitro and divided into four groups,control group, shikonin low dose group(10 μmol/L), shikonin medium dose group(20 μmol/L)and shikonin high dose group(40 μmol/L).CCK-8 method was used to detect the proliferation activity of A431 cells. Cell cycle and apoptosis were detected by PI staining and Annexin V-FITC/PI staining. The expression levels of PCNA and Cyclin B1 were detected by qRT-PCR. Western blot was used to detect the expressions of AKT and p-AKT in cells.Results:Shikonin could inhibit the proliferation of A431 cells in a time- and dose-dependent manner(P<0.001). Shikonin could block A431 cells in S phase and G2/M phase(P<0.001). And shikonin could induce apoptosis(P<0.001). The results of qRT-PCR showed that shikonin inhibited the expressions of PCNA and Cyclin B1 mRNA in A431 cells(P<0.001). Western blot analysis showed that shikonin could down-regulate the expression of p-AKT in cells(P<0.001).Conclusion:Shikonin can inhibit the growth of cutaneous squamous cell carcinoma cells, and the mechanism may be related to its inhibiting the activation of PI3K/AKT signaling pathway.

参考文献/References:

[1] MARUR S,FORASTIERE AA.Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment[J].Mayo Clinic Proceedings,2016,91(3):386
[2] SEIWERT TY,BURTNESS B,MEHRA R,et al.Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck(KEYNOTE-012):an open-label, multicentre, phase 1b trial[J].Lancet Oncol,2016,17(7):956
[3] 徐佳,伍春莲.紫草素药理作用研究进展[J].药物生物技术,2015,22(1):87
[4] LI Y,LU HL,GU YC,et al.Enhancement of NK cells proliferation and function by Shikonin[J].Immunopharmacol Immunotoxicol,2017,39(3):124
[5] 梁文全,陈凛,郗洪庆,等.紫草素在消化系统肿瘤中的抗癌机制研究进展[J].现代生物医学进展,2017,17(15):2964
[6] LIANG WQ,CUI JX,ZHANG KC,et al.Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer[J].Oncotarget,2017,8(65):109094
[7] LEE MJ,KAO SH,HUNAG JE,et al.Shikonin time-dependently induced necrosis or apoptosis in gastric cancer cells via generation of reactive oxygen species[J].Chem Biol Interact,2014,211(15):44
[8] 阮敏,杨雯君,周晓健,等.紫草素对口腔鳞癌Tca8113细胞增殖与凋亡的作用[J].中国口腔颌面外科杂志,2010,8(1):66
[9] FAN C,DONG Y,XIE Y,et al.Shikonin reduces TGF-β1-induced collagen production and contraction in hypertrophic scar-derived human skin fibroblasts[J].Int J Mol Med,2015,36(4):985
[10]李蒙娜,闫言,王宝玺.紫草素促进皮肤伤口愈合机制研究进展[J].中医药学报,2018,46(2):124
[11]PITMAN KT,JOHNSON JT.Skin metastases from head and neck squamous cell carcinoma:incidence and impact[J].Head Neck,2015,21(6):560
[12]杨延龙,张丞,纪荣,等.紫草素促进化疗药物渗漏局部皮肤组织损伤愈合的实验研究[J].上海中医药杂志,2011,45(7):60
[13]王汝兴,鲁艳杰,周健,等.紫草素对人卵巢癌细胞SKOV3细胞增殖和凋亡的影响[J].中药药理与临床,2016(2):76
[14]SHAHSAVARI Z,KARAMI-TEHRANI F,SALAMI SA.RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway[J].Tumor Biology,2016,37(4):4479
[15]KO H,KIM SJ,SHIM SH,et al.Shikonin induces apoptotic cell death via regulation of p53 and Nrf2 in ags human stomach carcinoma cells[J].Biomol Ther(Seoul),2016,24(5):501
[16]MARTINI M,DE SANTIS MC,BRACCINI L,et al.PI3K/AKT signaling pathway and cancer: an updated review[J].Ann Med,2014,46(6):372
[17]LIM HJ,CROWE P,YANG JL.Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer[J].J Cancer Res Clin Oncol,2015,141(4):671
[18]朱里,陈思远,林能兴,等.PI3K-Akt在皮肤鳞状细胞癌组织中的表达[J].中华皮肤科杂志,2010,43(9):649
[19]JURÍKOVÁ M,DANIHEL ,POLÁK ,et al.Ki67, PCNA, and MCM proteins: Markers of proliferation in the diagnosis of breast cancer[J].Acta Histochem,2016,118(5):544
[20]ROH M,SONG CS,KIM J,et al.Chromosomal instability induced by Pim-1 is passage-dependent and associated with dysregulation of cyclin B1[J].J Biol Chem,2005,280(49):40568
[21]YANG YY,HE HQ,CUI JH,et al.Shikonin derivative DMAKO-05 inhibits Akt signal activation and melanoma proliferation[J].Chem Biol Drug Des,2016,87(6):895
[22]WANG L,GAI P,XU R,et al.Shikonin protects chondrocytes from interleukin-1beta-induced apoptosis by regulating PI3K/Akt signaling pathway[J].Int J Clin Exp Pathol,2015,8(1):298

备注/Memo

备注/Memo:
【基金项目】四川省科技支撑计划基金资助项目(2015SZ0034)
【作者简介】赵菊花,通信作者,女,1977年4月9日生,博士,副主任医师,研究方向:皮肤与性病专业基础与临床,E-mail:214104642@qq.com
更新日期/Last Update: 2019-05-20