华西口腔医学杂志 ›› 2019, Vol. 37 ›› Issue (6): 583-588.doi: 10.7518/hxkq.2019.06.003
王京楠,樊亚萍,陈娇,冯云,崔博淼,李小英,王利伟,陈红利,张平,吴红崑()
收稿日期:
2019-03-16
修回日期:
2019-06-27
出版日期:
2019-12-01
发布日期:
2019-11-27
通讯作者:
吴红崑
E-mail:811120691@qq.com
作者简介:
王京楠,硕士,E-mail:373104721@qq.com
基金资助:
Wang Jingnan,Fan Yaping,Chen Jiao,Feng Yun,Cui Bomiao,Li Xiaoying,Wang Liwei,Chen Hongli,Zhang Ping,Wu Hongkun()
Received:
2019-03-16
Revised:
2019-06-27
Online:
2019-12-01
Published:
2019-11-27
Contact:
Hongkun Wu
E-mail:811120691@qq.com
Supported by:
摘要:
目的 探讨蛋白激酶D1(PKD1)在人口腔鳞癌细胞SCC-25生长、凋亡及化疗药物敏感性中的作用和机制。方法 转染control-shRNA和PKD1-shRNA质粒,建立PKD1基因沉默的SCC-25细胞系;CCK-8及流式细胞术检测PKD1基因沉默后细胞的增殖、凋亡及细胞对化疗药物紫杉醇的敏感性;Western blot检测凋亡相关蛋白Bax、Bcl-2及多药耐药蛋白P-gp的表达变化。结果 PKD1在口腔肿瘤细胞SCC-25、CAL-27、SACC-83中呈现高表达;PKD1基因沉默后SCC-25细胞内抗凋亡蛋白Bcl-2表达显著降低,细胞生长受到抑制,凋亡增加;多药耐药蛋白P-gp表达下调,紫杉醇半数抑制浓度及耐药指数明显降低。结论 PKD1通过调控SCC-25细胞内凋亡相关蛋白表达和多药耐药蛋白P-gp表达,调控SCC-25生长、凋亡和对药物敏感性,是口腔鳞癌细胞生物治疗潜在靶点。
中图分类号:
王京楠,樊亚萍,陈娇,冯云,崔博淼,李小英,王利伟,陈红利,张平,吴红崑. 蛋白激酶D1在调节口腔鳞癌细胞增殖、凋亡及药物敏感性中的作用[J]. 华西口腔医学杂志, 2019, 37(6): 583-588.
Wang Jingnan,Fan Yaping,Chen Jiao,Feng Yun,Cui Bomiao,Li Xiaoying,Wang Liwei,Chen Hongli,Zhang Ping,Wu Hongkun. Role of protein kinase D1 in regulating the growth, apoptosis and drug sensitivity of oral squamous carcinoma cells[J]. West China Journal of Stomatology, 2019, 37(6): 583-588.
[1] |
Guha S, Tanasanvimon S ,Sinnett-smith J, et al. Role of protein kinase D signaling in pancreatic cancer[J]. Biochem Pharmacol, 2010,80(12):1946-1954.
doi: 10.1016/j.bcp.2010.07.002 URL |
[2] |
Jaggi M, Du C, Zhang WG , et al. Protein kinase D1: a protein of emerging translational interest[J]. Front Biosci, 2007,12:3757-3767.
doi: 10.2741/2349 URL pmid: 17485336 |
[3] |
LaValle CR, George KM, Sharlow ER , et al. Protein kinase D as a potential new target for cancer therapy[J]. Biochim Biophys Acta, 2010,1806(2):183-192.
doi: 10.1016/j.bbcan.2010.05.003 URL pmid: 20580776 |
[4] |
Rykx A, De Kimpe L, Mikhalap S , et al. Protein kinase D: a family affair[J]. Febs Lett, 2003,546(1):81-86.
doi: 10.1016/s0014-5793(03)00487-3 URL pmid: 12829240 |
[5] |
Van Lint J, Rykx A, Maeda Y , et al. Protein kinase D: an intracellular traffic regulator on the move[J]. Trends Cell Biol, 2002,12(4):193-200.
doi: 10.1016/s0962-8924(02)02262-6 URL pmid: 11978539 |
[6] |
Rozengurt E, Rey O, Waldron RT . Protein kinase D signaling[J]. J Biol Chem, 2005,280(14):13205-13208.
doi: 10.1074/jbc.R500002200 URL pmid: 15701647 |
[7] |
Chiu TT, Leung WY, Moyer MP , et al. Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-kappaB[J]. Am J Physiol Cell Physiol, 2007,292(2):C766-C767.
doi: 10.1152/ajpcell.00308.2006 URL pmid: 16928771 |
[8] |
Sinnett-Smith J, Jacamo R, Kui R , et al. Protein kinase D mediates mitogenic signaling by Gq-coupled receptors through protein kinase C-independent regulation of activation loop Ser744 and Ser748 phosphorylation[J]. J Biol Chem, 2009,284(20):13434-13445.
doi: 10.1074/jbc.M806554200 URL pmid: 19289471 |
[9] |
Karam M, Bièche I, Legay C , et al. Protein kinase D1 regulates ERalpha-positive breast cancer cell growth response to 17beta-estradiol and contributes to poor prognosis in patients[J]. J Cell Mol Med, 2014,18(12):2536-2552.
doi: 10.1111/jcmm.12322 URL pmid: 25287328 |
[10] |
Sundram V, Chauhan SC, Jaggi M . Emerging roles of protein kinase D1 in cancer[J]. Mol Cancer Res, 2011,9(8):985-996.
doi: 10.1158/1541-7786.MCR-10-0365 URL |
[11] |
Karam M, Legay C, Auclair C , et al. Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway[J]. Exp Cell Res, 2012,318(5):558-569.
doi: 10.1016/j.yexcr.2012.01.001 URL pmid: 22245102 |
[12] |
Thomas H, Coley HM . Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein[J]. Cancer Control, 2003,10(2):159-165.
doi: 10.1177/107327480301000207 URL pmid: 12712010 |
[13] |
Stavrovskaya AA . Cellular mechanisms of multidrug resistance of tumor cells[J]. Biochemistry (Mosc), 2000,65(1):95-106.
URL pmid: 10702644 |
[14] |
Szakács G, Paterson JK, Ludwig JA , et al. Targeting multidrug resistance in cancer[J]. Nat Rev Drug Discov, 2006,5(3):219-234.
doi: 10.1038/nrd1984 URL pmid: 16518375 |
[15] |
Di Pietro A, Dayan G, Conseil G , et al. P-glycoprotein-mediated resistance to chemotherapy in cancer cells: using recombinant cytosolic domains to establish structure-function relationships[J]. Braz J Med Biol Res, 1999,32(8):925-939.
doi: 10.1590/s0100-879x1999000800001 URL pmid: 10454753 |
[16] |
Fardel O, Lecureur V, Guillouzo A . The P-glycoprotein multidrug transporter[J]. Gen Pharmacol, 1996,27(8):1283-1291.
doi: 10.1016/s0306-3623(96)00081-x URL pmid: 9304397 |
[17] |
Abolhoda A, Wilson AE, Ross H , et al. Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin[J]. Clin Cancer Res, 1999,5(11):3352-3356.
URL pmid: 10589744 |
[18] |
Juliano RL, Ling V . A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants[J]. Biochim Biophys Acta, 1976,455(1):152-162.
doi: 10.1016/0005-2736(76)90160-7 URL pmid: 990323 |
[19] |
Nabekura T, Hiroi T, Kawasaki T , et al. Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein[J]. Biomed Pharmacother, 2015,70:140-145.
doi: 10.1016/j.biopha.2015.01.007 URL pmid: 25776492 |
[20] |
Yi YJ, Jia XH, Wang JY , et al. Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1[J]. Int J Mol Med, 2016,37(5):1405-1411.
doi: 10.3892/ijmm.2016.2539 URL pmid: 27035504 |
[21] |
Ren J, Xu YY, Huang QH , et al. Chabamide induces cell cycle arrest and apoptosis by the Akt/MAPK pathway and inhibition of P-glycoprotein in K562/ADR cells[J]. Anticancer Drugs, 2015,26(5):498-507.
doi: 10.1097/CAD.0000000000000209 URL pmid: 25714087 |
[22] |
Ravna AW, Sager G . Molecular modeling studies of ABC transporters involved in multidrug resistance[J]. Mini Rev Med Chem, 2009,9(2):186-193.
doi: 10.2174/138955709787316065 URL pmid: 19200023 |
[23] |
Barancík M1, Bohácová V, Kvackajová J , et al. SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance[J]. Eur J Pharm Sci, 2001,14(1):29-36.
doi: 10.1016/s0928-0987(01)00139-7 URL pmid: 11457647 |
[24] |
Fujita T, Washio K, Takabatake D , et al. Proteasome inhibitors can alter the signaling pathways and attenuate the P-glycoprotein-mediated multidrug resistance[J]. Int J Cancer, 2005,117(4):670-682.
doi: 10.1002/ijc.21063 URL pmid: 15945097 |
[25] |
Shen HL, Xu WL, Luo WJ , et al. Upregulation of mdr1 gene is related to activation of the MAPK/ERK signal transduction pathway and YB-1 nuclear translocation in B-cell lymphoma[J]. Exp Hematol, 2011,39(5):558-569.
doi: 10.1016/j.exphem.2011.01.013 URL |
[26] |
Zhao L, Wang Y, Jiang LY , et al. MiR-302a/b/c/d cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein(P-gp) by targeting MAP/ERK kinase kinase 1 (MEKK1)[J]. J Exp Clin Cancer Res, 2016,35:25.
doi: 10.1186/s13046-016-0300-8 URL pmid: 26842910 |
[27] |
Yu C, Argyropoulos G, Zhang Y , et al. Neuroinflammation activates Mdr1b efflux transport through NF kappa B: promoter analysis in BBB endothelia[J]. Cell Physiol Biochem, 2008,22(5/6):745-756.
doi: 10.1159/000185558 URL pmid: 19088456 |
[28] |
Dai Y, Xie CH, Neis JP , et al. MicroRNA expression profiles of head and neck squamous cell carcinoma with docetaxel-induced multidrug resistance[J]. Head Neck, 2011,33(6):786-791.
doi: 10.1002/hed.21540 URL pmid: 21560177 |
[29] |
Kim M, Jang HR, Kim JH , et al. Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion[J]. Carcinogenesis, 2008,29(3):629-637.
doi: 10.1093/carcin/bgm291 URL pmid: 18283041 |
[30] |
Guha S, Rey O, Rozengurt E . Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synjournal in human pancreatic carcinoma cell line PANC-1[J]. Cancer Res, 2002,62(6):1632-1640.
URL pmid: 11912133 |
[31] |
Brasacchio D, Alsop AE, Noori T , et al. Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization[J]. Cell Death Differ, 2017,24(6):961-970.
doi: 10.1038/cdd.2016.119 URL pmid: 28060382 |
[32] |
McCubrey JA, Steelman LS, Chappell WH , et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance[J]. Biochim Biophys Acta, 2007,1773(8):1263-1284.
doi: 10.1016/j.bbamcr.2006.10.001 URL pmid: 17126425 |
[33] |
Paolucci L, Rozengurt E . Protein kinase D in small cell lung cancer cells: rapid activation through protein kinase C[J]. Cancer Res, 1999,59(3):572-577.
URL pmid: 9973202 |
[1] | 李修珍, 姜明, 张颖, 刘育含, 李帆, 曾飞, 马玉莹, 杨加震, 杨芳. 基于重水拉曼技术的白色念珠菌对变异链球菌代谢活性和耐药性影响的研究[J]. 华西口腔医学杂志, 2022, 40(2): 225-231. |
[2] | 王利伟,余宇,陈娇,冯云,崔博淼,李小英,王京楠,陈红利,张平. 蛋白激酶D1对口腔鳞癌细胞在肿瘤微环境中生长代谢的调控[J]. 华西口腔医学杂志, 2019, 37(6): 577-582. |
[3] | 杨文丽,孙明磊,张朋,余炜伟,周海霞,孙强. 下调性别决定区Y框蛋白9对口腔鳞癌细胞上皮间质转化及克隆能力的影响[J]. 华西口腔医学杂志, 2019, 37(1): 13-18. |
[4] | 贾洁茹 梁爽 刘济远 赵君 唐休发. 丝/苏氨酸蛋白激酶/哺乳动物雷帕霉素靶蛋白/p70 S6K信号通路在口腔鳞癌中的表达及临床意义[J]. 华西口腔医学杂志, 2014, 32(5): 504-508. |
[5] | 邬腊梅 杨宏宇 罗娟 苏铭扬. 4-1BBL-B7-H3基因对免疫重建重症联合免疫缺陷荷瘤鼠的抑瘤作用[J]. 华西口腔医学杂志, 2014, 32(2): 190-195. |
[6] | 蒋宁宁 巫家晓 卿海云 曹阳 杨亦萍. 口腔鳞癌淋巴结转移与丝裂原活化蛋白激酶激酶4基因表达的关系及其临床意义[J]. 华西口腔医学杂志, 2011, 29(05): 555-558. |
[7] | 魏魁杰 张雷 杨筱 韩伟 钟来平 叶冬霞 张志愿. 细胞角蛋白17在口腔鳞癌中的表达[J]. 华西口腔医学杂志, 2011, 29(04): 404-408. |
[8] | 陈思秀 李小玉 孔祥丽 冯云. 口腔鳞状细胞癌中血管内皮生长因子-C的表达及其与血管、淋巴管生成、淋巴结转移的关系[J]. 华西口腔医学杂志, 2010, 28(03): 319-323. |
[9] | 尹东 高志. 趋化因子受体CXCR4在口腔鳞癌中的表达和临床意义[J]. 华西口腔医学杂志, 2007, 25(04): 392-395. |
[10] | 冯戈 王大章 陈槐卿 何嘉 冷卫东. 体外诱导Tca8113细胞产生耐药性的分析[J]. 华西口腔医学杂志, 2007, 25(02): 184-187. |
[11] | 曹选平,张松涛,周弘,吴豪阳,刘学军,张媛媛. 口腔鳞癌中环氧合酶-2的表达与微血管密度的关系[J]. 华西口腔医学杂志, 2005, 23(05): 431-433. |
[12] | 武云霞,梁萍,南欣荣,焦艳军,孙晓军. 血管生成素在人口腔鳞癌的表达及意义[J]. 华西口腔医学杂志, 2005, 23(01): 63-64. |
[13] | 杨湛,普苹,温玉明,付红梅,李继梅. 口腔鳞癌浸润方式与颈淋巴结转移关系的组织学研究[J]. 华西口腔医学杂志, 2005, 23(01): 49-52. |
[14] | 唐恩溢,胡勤刚,周炳荣,杨旭东. 局部注射IL-2联合化疗对口腔鳞癌浸润淋巴细胞的影响[J]. 华西口腔医学杂志, 2003, 21(06): 444-446. |
[15] | 康非吾,吴正华,黄欣,温玉明,王昌美. 口腔鳞癌患者颈淋巴结cN_0的处理[J]. 华西口腔医学杂志, 2003, 21(04): 298-300. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||