您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (1): 17-21.doi: 10.6040/j.issn.1671-7554.0.2015.566

• 基础医学 • 上一篇    下一篇

索拉非尼对顺铂耐药性舌癌Tca8113/DDP细胞增殖及凋亡影响的体外研究

郝丽静1,葛树卿1,王淑芬1,郑文娇1,张斌2   

  1. 1.辽宁医学院, 辽宁 锦州 121001;
    2.辽宁医学院附属第一医院口腔科, 辽宁 锦州 121001
  • 收稿日期:2015-06-12 出版日期:2016-01-11 发布日期:2016-01-11
  • 通讯作者: 张斌. E-mail:18841609084@163.com E-mail:18841609084@163.com
  • 基金资助:
    辽宁省教育厅科学研究项目(05L141)

Effects of sorafenib on the proliferation and apoptosis of cisplatin-resistant tongue cancer cells in vitro

HAO Lijing1, GE Shuqing1, WANG Shufen1, ZHENG Wenjiao1, ZHANG Bin2   

  1. 1. Liaoning Medical University, Jinzhou 121001, Liaoning, China;
    2. Department of Dentistry, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, Liaoning, China
  • Received:2015-06-12 Online:2016-01-11 Published:2016-01-11

摘要: 目的 评价并探讨索拉非尼对顺铂耐药性舌癌(Tca8113/DDP)细胞增殖和凋亡的影响及其机制。 方法 采用顺铂连续作用并逐步提高药量的递增压力选择法,从人舌癌细胞(Tca8113)中分离出对顺铂耐药的细胞亚株(Tca8113/DDP);采用不同浓度的索拉非尼处理Tca8113/DDP细胞24、48、72 h,MTT法检测索拉非尼对Tca8113/DDP细胞增殖抑制的影响;用药后48 h,Annexin V-FITC/PI染色法流式细胞仪分别检测不同浓度索拉非尼对细胞凋亡的影响,Western blotting法检测不同浓度索拉非尼对细胞中舌癌耐药相关蛋白1(TCRP1)的影响。结果 索拉非尼处理细胞后,Tca8113/DDP细胞的增殖有明显的抑制作用,并且呈现一定的浓度和时间依赖关系。索拉非尼可以抑制TCRP1的表达,且有一定的剂量相关性。 结论 索拉非尼能显著抑制顺铂耐药性舌癌细胞的增殖并且诱导其凋亡,其机制可能与对TCRP1表达的影响有关。

关键词: 索拉非尼, 舌癌耐药相关蛋白1, 舌肿瘤

Abstract: Objective To explore the effects of sorafenib on the proliferation and apoptosis of cisplatin-resistant tongue cancer cells(Tca8113/DDP)and to investigate the possible mechanisms. Methods The Tca8113/DDP cells were separated by continuously exposing Tca8113 OSCC cells to a stepwise escalating concentration of cisplatin. The inhibitory effects of sorafenib on the proliferation of Tca8113/DDP cells were determined by MTT assay after Tca8113/DDP cells were treated with different concentrations of sorafenib for 24, 48 and 72 hours. The effects of sorafenib on the apoptosis of Tca8113/DDP cells were detected by flow cytometry of Annexin V-FITC/PI staining method. The expression level of Tongue cancer resistance associated protein 1(TCRP1)was detected by Western blotting after sorafenib treatment. Results The proliferation of Tca8113/DDP cells was significantly inhibited in a time-and concentration-dependent manner. Sorafenib could inhibit the expression of TCRP1 proteins in a concentration-dependent manner. Conclusion Sorafenib can significantly inhibit the proliferation of Tca8113/DDP cells and induce apoptosis. The mechanisms might be related with the effect of the expression of TCRP1.

Key words: Sorafenib, Tongue cancer resistance associated protein 1, Tongue neoplasms

中图分类号: 

  • R739.8
[1] Massano J, Regateiro FS, Januario G, et al. Oral squamous cell carcinoma: review of prognostic and predictive factors[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2006, 102(1): 67-76.
[2] Magrath I, Litvak J. Cancer in developing countries: opportunity and challenge[J]. J Natl Cancer Inst, 1993, 85(11): 862-874.
[3] Simons AL, Mattson DM, Dornfeld K, et al. Glucose deprivation induced metabolic oxidative stress and cancer therapy[J]. J Cancer Res Ther, 2009, 5 Suppl 1: S2-6.
[4] Zhu H, Liu Z, Tang L, et al. Reversal of P-gp and MRPI-mediated multidrug resistance by H6, a gypenoside aglycon from gynostemma pentaphyllum, in vincristine-resistant human oral cancer(KB/VCR)cells[J]. Eur J Pharmacol, 2012, 696(1-3): 43-53.
[5] Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer[J]. N Engl J Med, 2004, 350(4): 351-360.
[6] Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high risk squamous cell carcinoma of the head and neck[J]. N Engl J Med, 2004, 350(19): 1937-1944.
[7] 谷依学, 范莎莎, 王成坤, 等. TCRP1在口腔鳞癌中介导顺铂耐药的体内研究[J]. 中国药理学通报, 2012, 28(11): 1574-1578. GU Yixue, FAN Shasha, WANG Chengkun, et al. TCRP1 mediates the resistance of oral squamous cell carcinoma to cisplatin in vivo[J]. Chinese Pharmacological Bulletin, 2012, 28(11): 1574-1578.
[8] 谷依学, 王成坤, 尹江, 等. TCRP1通过PI3k-Akt途径介导口腔鳞癌顺铂化学治疗耐受[J]. 国际病理科学与临床杂志, 2012, 32(6): 461-468. GU Yixue, WANG Chengkun, YIN Jiang, et al. TCRP1 mediates the resistance of oral squamous cell carcinoma to cisplatin through regulation of PI3K-Akt pathway[J]. Int J Pathol Clin Med, 2012, 32(6): 461-468.
[9] Gu Y, Fan S, Xiong Y, et al. Cloning and functional characterization of TCRP1, a novel gene mediating resistance to cisplatin in an oral squamous cell carcinoma cell line[J]. FEBS Letters, 2011, 585(6): 881-887.
[10] Peng B, Gu Y, Xiong Y, et al. Microarray-assisted pathway analysis identifies MT1X & NFκB as mediators of TCRP1-associated resistance to cisplatin in oral squamous cell carcinoma[J]. PLoS One, 2012, 7(12): e51413.
[11] Sharma N, Pennell N, Nickolich M, et al. Phase II trial of sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer[J]. Invest New Drugs, 2014, 32(2): 362-368.
[12] Kim YB, Jeung HC, Jeong I, et al. Mechanism of enhancement of radiation-induced cytotoxicity by sorafenib in colorectal cancer[J]. J Radiat Res, 2013, 54(1): 52-60.
[13] Liu CY, Tseng LM, Su JC, et al. Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells[J]. Breast Cancer Res, 2013, 15(4): R63.
[14] Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK Pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5[J]. Cancer Res, 2006, 66(24): 11851-11858.
[15] Safarinejad MR. Safety and efficacy of sorafenib in patients with castrate resistant prostate cancer: a Phase II study[J]. Urol Oncol, 2010, 28(1): 21-27.
[16] Hsu FT, Chang B, Chiang IT, et al. Synergistic effect of sorafenib with ionizing radiation on human oral cancer cells[J]. In Vivo, 2014, 28(5): 925-934.
[1] 贺武斌,苏荣健. 白头翁皂苷D联合索拉非尼对人肝癌细胞侵袭与转移的影响[J]. 山东大学学报(医学版), 2016, 54(7): 18-22.
[2] 王振光,孙善珍,施琳,王东关. 舌鳞癌细胞Tca-8113与舌成纤维细胞间信号传导机制的研究[J]. 山东大学学报(医学版), 2007, 45(5): 446-449.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!