Met激酶抑制剂BMS-777607对舌鳞癌细胞CAL27增殖、凋亡的影响

doi:10.19439/j.sjos.2021.06.003

上海口腔医学 ›› 2021, Vol. 30 ›› Issue (6): 573-578.doi: 10.19439/j.sjos.2021.06.003

Met激酶抑制剂BMS-777607对舌鳞癌细胞CAL27增殖、凋亡的影响

马曌磊¹, 刘佳楠¹, 苏荣健², 贺武斌³, 黄克强¹

1.锦州医科大学附属第二医院·口腔医学院,辽宁锦州 121004;
2.锦州医科大学生命科学研究院,辽宁锦州 121001;
3.锦州医科大学附属第一医院,辽宁锦州 121001

收稿日期:2020-04-21 修回日期:2020-05-28 发布日期:2022-03-09
通讯作者: 黄克强,E-mail：hkq9@163.com
作者简介:马曌磊（1991-）,女,硕士研究生, E-mail：410238376@qq.com
基金资助:
辽宁省自然科学基金（2015020326）

Effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue cell line CAL 27 squamous cell carcinoma

MA Zhao-lei¹, LIU Jia-nan¹, SU Rong-jian², HE Wu-bin³, HUANG Ke-qiang¹

1. The Second Affiliated Hospital and College of Stomatology of Jinzhou Medical University. Jinzhou 121004;
2. Institute of Life Sciences, Jinzhou Medical University. Jinzhou 121001;
3. The First Affiliated Hospital of Jinzhou Medical University. Jinzhou 121001, Liaoning Province, China

Received:2020-04-21 Revised:2020-05-28 Published:2022-03-09

摘要/Abstract

摘要： 目的: 探讨Met激酶抑制剂BMS-777607对人舌鳞状细胞癌（鳞癌）CAL27细胞增殖、凋亡的影响。方法: 采用MTT、克隆形成实验及EdU细胞成像实验,检测BMS-777607对CAL27细胞增殖的影响。通过Heochst33342染色,观察BMS-777607对CAL27细胞的凋亡形态变化。采用JC-1染色,检测BMS-777607对CAL27细胞线粒体膜电位变化。采用Western免疫印迹检测BMS-777607对CAL27细胞中增殖蛋白Akt、p-Akt,凋亡相关蛋白Bcl-2、Cleaved caspase-3、Bax、Parp表达的影响。采用SPSS 22.0软件包对数据进行统计学分析。结果: BMS-777607抑制CAL27细胞增殖,促进其凋亡,呈浓度依赖性（P<0.05）。BMS-777607抑制Bcl-2、p-Akt表达,促进Bax、Cleaved caspase-3、Parp蛋白表达（P<0.05）。结论: BMS-777607能够抑制CAL27细胞增殖并促进其凋亡。

关键词: Met激酶, BMS-777607, 舌鳞癌, CAL27细胞, 凋亡

Abstract: PURPOSE: To investigate the effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue squamous cell carcinoma cell line CAL27. METHODS: The effect of BMS-777607 on proliferation of CAL27 was detected by MTT method, clone formation assay and EdU cell imaging. Morphological changes of apoptosis of CAL27 cells induced by BMS-777607 were observed by Heochst33342 staining. JC-1 staining was used to detect the changes of mitochondrial membrane potential of CAL27 cells treated with BMS-777607. Western blot was used to detect the effect of BMS-777607 on the expression of proliferation protein Akt, p-Akt and apoptosis-related proteins Bcl-2, Cleaved caspase-3, Bax and Parp in CAL27 cells. The data were analyzed using SPSS 22.0 software package. RESULTS: BMS-777607 inhibited proliferation and promoted apoptosis of CAL27 cells in a concentration-dependent manner（P<0.05）. It also inhibited the expression of Bcl-2 and p-Akt and promoted the expression of Bax, Cleaved caspase-3 and Parp protein (P<0.05). CONCLUSIONS: BMS-777607 can inhibit proliferation and promote apoptosis of CAL27 cells.

Key words: Met kinase, BMS-777607, Tongue squamous cell carcinoma, CAL27, Apoptosis

中图分类号:

R739.8

马曌磊, 刘佳楠, 苏荣健, 贺武斌, 黄克强. Met激酶抑制剂BMS-777607对舌鳞癌细胞CAL27增殖、凋亡的影响[J]. 上海口腔医学, 2021, 30(6): 573-578.

MA Zhao-lei, LIU Jia-nan, SU Rong-jian, HE Wu-bin, HUANG Ke-qiang. Effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue cell line CAL 27 squamous cell carcinoma[J]. Shanghai Journal of Stomatology, 2021, 30(6): 573-578.

参考文献

[1] Rivera C.Essentials of oral cancer[J]. Int J Clin Exp Pathol, 2015, 8(9): 11884-11894.
[2] He Q, Chen Z, Cabay RJ, et al.MicroRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection[J]. Oral Oncol, 2016, 57(1): 15-20.
[3] Gu Y, Liu H, Kong F, et al.Mir-22 /KAT6B axis is a chemotherapeutic determiner via regulation of PI3k-Akt-NF-kB pathway in tongue squamous cell carcinoma[J]. J Exp Clin Cancer Res, 2018, 37(1): 164-177.
[4] Schroeder GM, An Y, Cai ZW, et al.Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607),a selective and orally efficacious inhibitor of the Met kinase superfamily[J]. J Med Chem,2009, 52(5): 1251-1254.
[5] Dai Y, Siemann DW.BMS-777607, a small-molecule Met kinase inhibitor,suppresses hepatocyte growth factor-stimulated prostate cancer metastatic phenotype[J]. Mol Cancer Ther, 2010, 9(6): 1554-1561.
[6] Hu CY, Xu XM, Hong B, et al.Aberrant RON and MET co-overexpression as novel prognostic biomarkers of shortened patient survival and therapeutic targets of tyrosine kinase inhibitors in pancreatic cancer[J]. Front Oncol, 2019, 9: 1377-1392.
[7] Siegel RL, Miller KD, Jemal A.Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1): 7-30.
[8] Yu GT, Bu LL, Huang C, et al.PD-1 blockade attenuates immunosuppressive myeloid cells due to inhibition of CD47/SIRPα axis in HPV negative head and neck squamous cell carcinoma[J]. Oncotarget, 2015, 6(39): 42067-42080.
[9] Yu X, Li Z.MicroRNA expression and its implications for diagnosis and therapy of tongue squamous cell carcinoma[J]. J Cell Mol Med, 2016, 20(1): 10-16.
[10] Ko SY, Lin SC, Wong YK, et al.Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma[J]. Cancer Lett, 2007, 245(1-2): 33-43.
[11] Chang K, Karnad A, Zhao S, et al.Roles of c-Met and RON kinases in tumor progression and their potential as therapeutic targets[J]. Oncotarget, 2015, 6(6): 3507-3518.
[12] Sharma S, Zeng ZJ, Zhuang CM, et al.Small-molecule inhibitor BMS-777607 induces breast cancer cell polyploidy with increased resistance to cytotoxic chemotherapy agents[J]. Mol Cancer Ther, 2013, 12(5): 725-736.
[13] Very N, Vercoutter-Edouart AS, Lefebvre T, et al.Cross-dysregulation of O -GlcNAcylation and PI3K/AKT/mTOR axis in human chronic diseases[J]. Front Endocrinol (Lausanne), 2018, 9: 602-611.
[14] McKinzie BP, Bulliington WM, Mazur JE, et al. Efficacy of short-course, low-dose corticosteroid therapy for acute pulmonary sarcoidosis exacerbations[J]. Am J Med Sci, 2010, 339(1): 1-4.
[15] Faham N, Zhao L, Welm AL. mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential[J]. NPJ Breast Cancer, 2018, 4(1): 641-650.
[16] Ma JC,Sun XW,Su H,et al.Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer[J].World J Gastroenterol, 2017, 23(28): 5167-5178.
[17] 辛敏, 陈健, 郭艳红, 等. 异黄酮对膀胱癌细胞凋亡和PI3K/Akt信号通路的影响[J]. 广东医学, 2015, 36(5): 690-693.
[18] Liu LS, Bai XQ, Gao Y, et al.PCSK9 promotes oxLDL-Induced PC12 cell apoptosis through the Bcl-2/Bax-Caspase 9/3 signaling pathway[J]. Alzheimers Dis, 2017, 57(3): 723-734.
[19] Fulda S.Targeting apoptosis for anticancer therapy[J]. Semin Cancer Biol, 2015, 31(1): 84-88.
[20] Derakhshan A, Chen Z, Van Waes C.Therapeutic small molecules target inhibitor of apoptosis proteins in cancers with deregulation of extrinsic and intrinsic cell death pathways[J]. Clin Cancer Res, 2017, 23(6): 1378-1387.

Met激酶抑制剂BMS-777607对舌鳞癌细胞CAL27增殖、凋亡的影响

Effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue cell line CAL 27 squamous cell carcinoma

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	李欣然, 陈霖, 孟箭. 斑蝥酸钠对人舌鳞癌CAL27细胞的抑制作用及机制研究[J]. 上海口腔医学, 2024, 33(3): 229-234.
[2]	沈忆芬, 刘超, 汤颖, 杨涛, 顾永春. ROS/JNK/caspase 3信号轴在薄荷味电子烟烟液诱导牙周膜干细胞凋亡中的作用[J]. 上海口腔医学, 2024, 33(1): 40-48.
[3]	刘芸, 陈浩月, 米静, 王菲菲, 万光勇, 崔超. 芍药苷对舌鳞癌CAL27细胞的抑制作用及机制探讨[J]. 上海口腔医学, 2023, 32(6): 597-602.
[4]	李胜男, 崔飞艳, 赵姗, 杜琛, 孟箭. 柯里拉京体内外诱导口腔鳞癌CAL-27细胞凋亡及机制探讨[J]. 上海口腔医学, 2023, 32(5): 462-467.
[5]	刘岩, 单丹妮, 孙晶, 邹雨希, 袁长永. Let-7a对人牙髓干细胞增殖、凋亡和成骨分化的影响[J]. 上海口腔医学, 2023, 32(5): 468-474.
[6]	杨恩黎, 王娜, 李名扬, 李易铭, 耿一鸣, 张东升, 吴海威. 紫草素对血管瘤内皮细胞增殖、凋亡、迁移及成血管的影响[J]. 上海口腔医学, 2022, 31(6): 576-580.
[7]	叶璞, 黄兴鸿, 张伟, 吴萌, 俞辉明. cN0期舌鳞癌患者颈淋巴结转移的相关因素及预后分析[J]. 上海口腔医学, 2022, 31(5): 540-543.
[8]	李梦, 孙晋虎, 孟箭. 青蒿琥酯对人舌鳞癌CAL27细胞的体外抑制作用[J]. 上海口腔医学, 2022, 31(1): 32-37.
[9]	汤颖, 沈忆芬, 刘超, 邱吟枫, 顾永春, 于金华. 高浓度氟对人牙周膜干细胞凋亡的影响[J]. 上海口腔医学, 2021, 30(4): 360-366.
[10]	田一弘, 刘美希, 张强, 夏晨蕾, 阎潇, 袁晓. 周期性机械应力诱导的自噬抑制caspase通路依赖的成肌细胞凋亡[J]. 上海口腔医学, 2020, 29(3): 231-236.
[11]	徐竹青, 张馨予, 王少如, 李涛, 董刚, 李凤梅, 郑建金, 王云英, 徐晓娜. 人骨髓间充质干细胞对舌鳞癌细胞系Cal-27侵袭作用的影响[J]. 上海口腔医学, 2020, 29(2): 155-161.
[12]	蒋泱泱, 徐斌, 房兵. 凋亡相关基因在牙龈瘤中的特征性表达[J]. 上海口腔医学, 2020, 29(1): 31-35.
[13]	高磊, 孙智辉, 于浩, 井建鑫, 徐仲秋, 李潇, 张楠. 乳酸菌E6-1对人口腔癌细胞Cal-27体外增殖的抑制作用及机制探讨[J]. 上海口腔医学, 2019, 28(6): 605-609.
[14]	郎淼杰, 区跃坚. 唑来膦酸对成纤维细胞作用的影响[J]. 上海口腔医学, 2019, 28(5): 490-493.
[15]	康剑勇, 何娟, 段晓峰. 尼古丁对舌鳞状细胞癌Cal27细胞的生物学影响[J]. 上海口腔医学, 2019, 28(4): 368-372.