[1]陈彦洁,柳传毅,吕满霞,等.鱼藤素诱导肺癌细胞凋亡和细胞周期阻滞的分子机制[J].中国药理学通报,2019,(08):1109-1114.[doi:10.3969/j.issn.1001-1978.2019.08.015]
 CHEN Yan-jie,LIU Chuan-yi,LYU Man-xia,et al.Molecular mechanism of deguelin-induced apoptosis and cell cycle arrest in lung cancer cells in vitro[J].Chinese Pharmacological Bulletin,2019,(08):1109-1114.[doi:10.3969/j.issn.1001-1978.2019.08.015]
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鱼藤素诱导肺癌细胞凋亡和细胞周期阻滞的分子机制()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年08期
页码:
1109-1114
栏目:
论著
出版日期:
2019-08-14

文章信息/Info

Title:
Molecular mechanism of deguelin-induced apoptosis and cell cycle arrest in lung cancer cells in vitro
文章编号:
1001-1978(2019)08-1109-06
作者:
陈彦洁12柳传毅2吕满霞2方琼彤2吴新荣12
1.中国人民解放军南部战区总医院药剂科,广东,广州 510010; 2.华南理工大学食品科学与工程学院,广东,广州 510641
Author(s):
CHEN Yan-jie12 LIU Chuan-yi2 LYU Man-xia2 FANG Qiong-tong2 WU Xin-rong12
1.Dept of Pharmacy, General Hospital of Southern Theatre Command of PLA, Guangzhou 510010,China; 2.School of Food Science and Engineering, South China University of Technology,Guangzhou 510641,China
关键词:
鱼藤素 H1299细胞 细胞周期 抗肿瘤 Cyclin D1 CDK4/CDK6
Keywords:
deguelin H1299 cells cell cycle anti-tumor Cyclin D1 CDK4/CDK6
分类号:
R329.25; R329.28; R394.2; R734.202.2; R977.3; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.08.015
文献标志码:
A
摘要:
目的 探究鱼藤素是否能够阻滞细胞周期和细胞迁移,抑制非小细胞肺癌细胞的增殖。方法 鱼藤素(1.5625、3.125、6.25、12.5、25、50 μmol·L-1)处理H1299细胞不同时间后,CCK-8法检测细胞存活率,划痕实验测定划痕宽度及愈合率; 鱼藤素(1.5、3、6 μmol·L-1)处理24 h,PI单染测定细胞周期,Annexin V-FITC/PI双染检测凋亡率,qPCR检测药物处理后的H1299细胞中CDK4、CDK6和CCND1的基因表达情况。结果 鱼藤素能够降低H1299细胞的存活率,作用24、48、72 h的IC50值分别为(5.47±0.97)、(4.01±0.45)、(2.86±0.19)μmol·L-1,并抑制细胞的迁移与愈合能力。PI单染流式细胞术检测到其能阻滞细胞周期,使细胞阻滞在G0/G1期,流式双染实验测得其可诱导细胞的凋亡,qPCR发现鱼藤素可下调CDK4、CDK6和CCND1的基因表达。结论 鱼藤素可抑制H1299细胞的增殖,抑制细胞的运动迁移能力,阻滞细胞周期,诱导细胞凋亡,且鱼藤素可通过下调细胞周期调控系统中的CDK4、CDK6、CCND1基因表达来调控细胞周期,达到抗肿瘤作用。
Abstract:
Aim To explore whether deguelin can block cell cycle and cell migration, inhibit the proliferation of non-small cell lung cancer cells.Methods H1299 cells were treated with 1.562 5, 3.125, 6.25, 12.5, 25, 50 μmol·L-1 deguelin for different time(24, 48, 72 h); cell viability was detected by CCK-8 assay, and cell migration ability was tested by scratch assay.H1299 cells were treated with 1.5, 3, 6 μmol·L-1 deguelin for 24 h.Flow cytometry with PI single staining and Annexin V-FITC/PI double staining experiment were used to evaluate cell cycle and apoptosis.qPCR was used to detect the regulatory effects of deguelin and its carbamate derivative on the Cyclin D-CDK4/6 complex at the gene level.Results Deguelin inhibited cell growth and the IC50 value of deguelin was(5.47±0.97),(4.01±0.45),(2.86±0.19)μmol·L-1 when treated with 24, 48, 72 h respectively.Deguelin also inhibited the healing ability of H1299 cells and the migration of H1299 cells significantly(P<0.05).Deguelin could block H1299 cell cycle in G1 phase.Flow cytometry combined with Annexin V-FITC/PI double staining showed that deguelin could induce apoptosis of H1299 cells.qPCR experiments showed that deguelin could down-regulate the expression of CDK4, CDK6 and Cyclin D1 genes significantly(P<0.05).Conclusions Deguelin may regulate cell cycle by down-regulating CDK4, CDK6 and Cyclin D1 genes in the cell cycle regulation system, and reduce the migration ability of tumor cells to induce apoptosis.

参考文献/References:

[1] Wang Y, Ma W, Zheng W.Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention.[J].Mol Clin Oncol, 2013, 1(2):215-9.
[2] Lee H Y, Oh S H, Woo J K, et al.Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis[J].J Natl Cancer Inst, 2005, 97(22): 1695-9.
[3] Murillo G, Kosmeder J W, Pezzuto J M, et al.Deguelin suppresses the formation of carcinogen-induced aberrant crypt foci in the colon of CF-1 mice[J].Int J Cancer, 2003, 104(1): 7-11.
[4] Robles A J, Cai S, Cichewicz R H, et al.Selective activity of deguelin identifies therapeutic targets for androgen receptor-positive breast cancer[J].Breast Cancer Res Treat, 2016, 157(3): 475-88.
[5] Rebolleda N, Losada-Fernandez I, Perez-Chacon G, et al.Synergistic activity of deguelin and fludarabine in cells from chronic lymphocytic leukemia patients and in the new zealand black murine model[J].PLoS One, 2016, 11(4):154-9.
[6] Lee H Y.Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells[J].Biochem Pharmacol, 2004, 68(6):1119-24.
[7] Xu H, Li X, Ding W,et al.Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway[J].Cancer Cell Int, 2015, 15(1):25.
[8] Jia H, Ye H Y, Fu A, et al.Deguelin-an inhibitor to tumor lymphangiogenesis and lymphatic metastasis by downregulation of vascular endothelial cell growth factor-D in lung tumor model[J].Int J Cancer, 2010, 127(10):2455-66.
[9] Peng X H, Karna P, O'Regan R M, et al.Down-regulation of inhibitor of apoptosis proteins by deguelin selectively induces apoptosis in breast cancer cells[J].Mol Pharmacol, 2007, 71(1): 101-11
[10] Boreddy S R, Srivastava S K.Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting epithelial-to-mesenchymal transition in an orthotopic model[J].Oncogene, 2013, 32(34): 3980-91.
[11] Yang Y, Ji C, Bi Z, et al.Deguelin induces both apoptosis and autophagy in cultured head and neck squamous cell carcinoma cells[J].PLoS One, 2013, 8(1): 536-47.
[12] Kang H W, Kim J M, Cha M Y, et al.Deguelin, an Akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice[J].Dig Dis Sci, 2012, 57(11): 2873-82.
[13] Mehlen P, Puisieux A.Metastasis: a question of life or death[J].Nat Rev Cancer, 2006, 6(6):449-58.
[14] 董 杨,季 光,施建蓉,等.橘红素上调Cyclin B1和抑制ERK磷酸化诱导人胃癌AGS细胞周期阻滞[J].中国药理学通报, 2012,28(6):823-7.
[14] Dong Y,Ji G,Shi J R,et al.Arrest of human gastric cancer AGS cells by tangeretin via CyclinB1 upregulation and inhibition of ERK phosphorylation[J].Chin Pharmacol Bull, 2012,28(6):823-7.
[15] 李敬美,丁圆媛,潘夕春,等.细胞周期调节因子基因在H9c2心肌细胞肥大过程中的时相性表达变化[J].中国药理学通报, 2017,33(1):63-8.
[15] Li J M, Ding Y Y, Pan X C,et al.Temporal expressions of cell cycle regulators mRNA during hypertrophic process of H9c2 rat cardiomyocytes induced by angiotensinⅡ[J].Chin Pharmacol Bull, 2017,33(1):63-8.
[16] Malumbres M, Barbacid M.To cycle or not to cycle: a critical decision in cancer[J].Nat Rev Cancer, 2001, 1(3):222-31.
[17] Shapiro G I.Cyclin-dependent kinase pathways as targets for cancer treatment [J].J Clin Oncol, 2006, 24(11):1770-83.

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备注/Memo

备注/Memo:
收稿日期:2019-03-10,修回日期:2019-04-22
基金项目:全军后勤科研计划项目(No CGZ14C003)
作者简介:陈彦洁(1994-),女,硕士生,研究方向:糖类药物制备与研究,E-mail:444982911@qq.com;
吴新荣(1959-),女,硕士,主任药师,博士生导师,研究方向:中药筛选及药理学,通讯作者,E-mail:gzwxrong@yahoo.com
更新日期/Last Update: 2019-08-14