冬凌草甲素对人食管鳞癌细胞系KYSE-150和KYSE-450增殖及迁移的影响

doi:10.16098/j.issn.0529-1356.2019.05.010

解剖学报 ›› 2019, Vol. 50 ›› Issue (5): 601-607.doi: 10.16098/j.issn.0529-1356.2019.05.010

冬凌草甲素对人食管鳞癌细胞系KYSE-150和KYSE-450增殖及迁移的影响

黄坷坷^1,2,3刘玉珍^1,2,3陈彦民¹陈智¹ 刘丹辉¹赵宝生^1,2*

1.新乡医学院第一附属医院胸外科，河南卫辉 53100； 2.新乡医学院食管癌研究所，河南卫辉 453100； 3.新乡医学院第一附属医院河南省神经病学研究所，河南卫辉 453100

收稿日期:2018-08-15 修回日期:2018-10-26 出版日期:2019-10-06 发布日期:2019-12-10
通讯作者: 赵宝生 E-mail:drbszhao@xxmu.edu.cn
基金资助:
miR-212和人食管癌转移的相关性及其作用机制的研究;新乡医学院第一附属医院博士基金

Inhibitory effect of oridonin on proliferation and migration of human esophageal squamous cancer cell lines KYSE-150 and KYSE-450

HUANG Ke-ke ^1,2,3 LIU Yu-zhen ^1,2,3 CHEN Yan-min¹ CHEN Zhi¹ LIU Dan-hui¹ ZHAO Bao-sheng ^1,2*

1.Department of Thoracic Surgery, the First Affiliated Hospital of Xinxiang Medical University, He’nan Weihui 453100, China; 2.Esophageal Cancer Institute of Xinxiang Medical University, He’nan Weihui 453100, China; 3.He’nan Neurology Institute at the First Affiliated Hospital of Xinxiang Medical University, He’nan Weihui 453100, China

Received:2018-08-15 Revised:2018-10-26 Online:2019-10-06 Published:2019-12-10
Contact: ZHAO Bao-sheng E-mail:drbszhao@xxmu.edu.cn

摘要/Abstract

摘要：

目的探讨冬凌草甲素（ORI）对食管鳞癌细胞系KYSE-150和KYSE-450增殖、凋亡、周期及迁移的作用。方法 MTT法检测ORI对食管癌细胞增殖的影响；集落形成实验检测ORI对集落形成的影响；流式细胞术检测ORI对食管癌细胞凋亡和周期的影响；Transwell迁移实验检测ORI对食管癌细胞迁移的作用；Western blotting检测ORI对抗凋亡蛋白Bcl-2、细胞周期抑制蛋白p21Cip1/Waf1及上皮-间质转化（EMT）标志蛋白表达水平的影响。结果 ORI对KYSE-150和KYSE-450细胞的增殖、迁移和集落形成有显著的抑制作用（P<0.05），且抑制作用呈一定的时间、剂量依赖性；流式结果显示，随着ORI浓度的增加，细胞的凋亡率明显增加（P<0.05），G₂/M期细胞比例显著增加（P<0.05），G₀/G₁期细胞比例明显下降（P<0.05）；ORI处理食管癌细胞48 h，Bcl-2、间质细胞标志蛋白，波形蛋白（vimentin）、β-连环蛋白（β-catenin）表达下调，p21Cip1/Waf1、上皮细胞标志蛋白，E-钙黏蛋白（E-cadherin）表达上调。结论冬凌草甲素可能通过诱导细胞凋亡，阻滞细胞在G₂/M期抑制食管癌细胞的增殖，并通过抑制EMT转化从而抑制食管癌细胞的迁移。

关键词: 食管鳞癌细胞, 冬凌草甲素, 增殖, 迁移, 流式细胞术, 人

Abstract:

Objective To explore the effect of oridonin (ORI) on proliferation, apoptosis, cell cycle and migration of esophageal squamous carcinoma cell (ESCC) lines KYSE-150 and KYSE-450. Methods The effect of ORI on the proliferation and clony formation of esophageal cancer cells were detected by MTT and colony formation assays. Flow cytometry was performed to examine the impact of ORI on cell apoptosis and cell cycle. Transwell assay was applied to detect the role of ORI on cell migration. The effect of ORI on the expression of anti-apoptotic protein Bcl-2, cell cycle inhibitory protein p21Cip1/Waf1, epithelialmesenchymal transition (EMT) related markers were examined by Western blotting. Results ORI had a significant inhibitory effect on the proliferation, migration and clone formation of KYSE-150 and KYSE-450 cells (P<0.05) in a time and dose-dependent manner. With the increase of ORI concentration, apoptosis rate and the proportion of cells in G₂/M phase increased significantly (P<0.05), and the proportion of cells in G₀/G₁ phase decreased significantly (P<0.05). Bcl-2, vimentin and β-catenin were down-regulated and p21Cip1/Waf1, E-cadherin were up-regulated after treatment of ORI on ESCC cells for 48 hours. Conclusion ORI may inhibit ESCC cell proliferation and clony formation by inducing apoptosis and resting cells in G₂/M phase, and suppress ESCC cell migration via inhibiting EMT process.

Key words: Esophageal squamous carcinoma cell, Oridonin, Proliferation, Migration, Flow cytometry, Human

黄坷坷刘玉珍陈彦民陈智刘丹辉赵宝生. 冬凌草甲素对人食管鳞癌细胞系KYSE-150和KYSE-450增殖及迁移的影响[J]. 解剖学报, 2019, 50(5): 601-607.

HUANG Ke-ke LIU Yu-zhen CHEN Yan-min CHEN Zhi LIU Dan-hui ZHAO Bao-sheng. Inhibitory effect of oridonin on proliferation and migration of human esophageal squamous cancer cell lines KYSE-150 and KYSE-450[J]. Acta Anatomica Sinica, 2019, 50(5): 601-607.

参考文献

［1］ Zhou GB, Chen SJ, Wang ZY, et al. Back to the future of oridonin: again, compound from medicinal herb shows potent antileukemia efficacies in vitro and in vivo［J］. Cell Res, 2007, 17(4): 274-276.

［2］ Li DH, Han T, Liao J, et al. Oridonin, a promising ent-kaurane diterpenoid lead compound［J］. Int J Mol Sci, 2016, 17(9):1395-1413.

［3］ Owona BA, Schluesener HJ. Molecular Insight in the Multifunctional Effects of Oridonin［J］. Drugs RD, 2015, 15(3): 233-244.

［4］ Guo JT, Huang JK, Zhou Y, et al. Germline and somatic variations influence the somatic mutational signatures of esophageal squamous cell carcinomas in a Chinese population［J］. BMC Genomics, 2018, 19(1):538-551.

［5］ Tanaka Y, Yoshida K, Suetsugu T, et al. Recent advancements in esophageal cancer treatment in Japan［J］. Ann Gastroenterol Surg, 2018, 2(4):253-265.

［6］ Cai DT, Jin H, Xiong QX, et al. ER stress and ASK1-JNK activation contribute to oridonin induced apoptosis and growth inhibition in cultured human hepatoblastoma HuH-6 cells［J］. Mol Cell Biochem, 2013, 379(1-2):161-169.

［7］ Wang TX, Liu YH, Shi XY. Oridonin induces apoptosis of HepG2 cells via downregulating STAT3-HKⅡ pathway［J］. Chinese Pharmacological Bulletin, 2014, 30(3):397-402. (in Chinese)

王天晓, 刘迎滑, 时小燕. 冬凌草甲素下调 STAT3-HKⅡ 通路诱导 Hep G2 细胞凋亡的研究［J］. 中国药理学通报, 2014, 30(3):397-402.

［8］ Peng L, Xue RY, Gu ZhL, et al. The inhibitory and apoptosis effect of Oridonin on human lung adenocarcinoma SPC-A-1［J］. Chinese Pharmacological Bulletin,2010,26(4):558-559. (in Chinese)

彭蕾, 薛仁宇, 顾振纶, 等. 冬凌草甲素对人肺腺癌细胞株 SPC-A-1 增殖和凋亡的影响［J］. 中国药理学通报, 2010, 26(4):558-559.

［9］ Shi M, Lu XJ, Zhang J, et al. Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms［J］. Oncotarget, 2016, 7(16):22623-22631.

［10］Yang J, Ren XY, Zhang LP, et al. Oridonin inhibits oral cancer growth and PI3K/Akt signaling pathway［J］. Biomed Pharmacother, 2018, 100:226-232.

［11］Gu ZM, Wang XH, Qi R, et al.Oridonin induces apoptosis in uveal melanoma cells by upregulation of Bim and downregulation of fatty acid synthase［J］. Biochem Biophys Res Commun, 2015, 457(2):187-193.

［12］Huang WC, Huang MC, Ouyang H, et al. Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation［J］. Eur J Pharmacol, 2018, 826:133-139.

［13］Li JS, Bao LP, Zha DQ, et al. Oridonin protects against the inflammatory response in diabetic nephropathy by inhibiting the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways［J］. Int Immunopharmacol, 2018, 55:9-19.

［14］Zeng R, Chen Y, Zhao S, et al. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1［J］. Acta Pharmacol Sin, 2012, 33(1):91-100.

［15］Lu Y, Sun Y, Zhu JW, et al.Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway［J］. Cell Death Dis, 2018, 9(1):15-31.

［16］Liu Y, Liu YZ, Zhang RX, et al. Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/β-catenin signaling［J］. Int J Oncol, 2014, 45(2):795-803.

［17］Wu LP, Xu LY, Hu XF, et al. Effect of cod skin oligopeptide on the proliferation and apoptosis in human gastric cancer cells line SGC-7901 and its mechanism［J］. Acta Anatomica Sinica, 2017, 48(6):698-703. (in Chinese)

吴丽萍, 续力云, 胡晓斐, 等. 鳕鱼皮寡肽对人胃癌细胞 SGC-7901增殖凋亡的影响及机制［J］. 解剖学报, 2017, 48(6):698-703.

［18］Prieto-García E, Díaz-García CV, García-Ruiz Ⅰ, et al. Epithelial-to-mesenchymal transition in tumor progression［J］. Med Oncol, 2017, 34(7):122.

［19］Liu QQ, Chen K, Ye Q, et al. Oridonin inhibits pancreatic cancer cell migration and epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling pathway［J］. Cancer Cell Int, 2016, 16:57-65.

［20］Ma YC, Ke Y, Zi XL, et al. Induction of the mitochondria-mediated apoptosis in human esophageal cancer cells by DS2, a newly synthetic diterpenoid analog, is regulated by Bax and caused by generation of reactive oxygen species［J］. Oncotarget, 2016, 7(52):86211-86224.

［21］Chen W, Zhou JC, Wu KJ, et al. Targeting XBP1-mediated β-catenin expression associated with bladder cancer with newly synthetic Oridonin analogues［J］. Oncotarget, 2016, 7(35):56842-56854.

［22］Zhang HP, Li GQ, Guo WZ, et al. Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway［J］. Oncotarget, 2017, 8(63):106833-106843.

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冬凌草甲素对人食管鳞癌细胞系KYSE-150和KYSE-450增殖及迁移的影响

Inhibitory effect of oridonin on proliferation and migration of human esophageal squamous cancer cell lines KYSE-150 and KYSE-450

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