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尼妥珠单抗联合X射线照射对肺腺癌细胞A549的作用 被引量:4

The Impact of Nimotuzumab (hR-3) Combined with Radiation on Human Pulmonary Adenocarcinoma A549 Cells
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摘要 目的:探讨表皮生长因子(Epidermal growth factor receptor,EGFR)受体抑制剂尼妥珠单抗(h-R3)联合X射线照射,对肺腺癌细胞系的A549细胞的作用。方法:肺腺癌细胞系A549细胞常规培养48 h后,分为对照组,单纯h-R3组,单纯照射组,h-R3联合照射组。h-R3组分别以终浓度0.5、5、50、100、1 000 μg/mL处理后继续培养24 h.照射组采用Varian-6MV直线加速器X射线照射2、4、8、10Gy后继续培养24 h;h-R3联合照射组在照射前以50 μg/mL浓度h-R3处理后继续培养24 h。收集各组细胞进行甲基噻唑基四唑(MTT)法检测。测定细胞的光密度值(Optical Density,OD),绘制细胞存活情况,并在倒置显微镜下观察细胞形态变化。结果:对照组A549细胞的OD值为0.7867±0.0764,不同浓度h-R3组的OD值分别为0.793 6±0.0846,0.823 4±0.0688,0.760 3±0.057 3,0.790 2+0.063 7,0.820 8±0.0770,与对照组比较无明显差异(P>0.05);不同剂量照射组OD值分别为0.246 0±0.023 1,0.330 8±0.0336,0.343 0±0.0281,0.3175±0.0307,明显低于对照组(P<0.05);50 μg/mL浓度h-R3联合不同剂量照射组OD值分别为0.192 3±0.014 6,0.231 8±0.020 6,0.293 0±0.024 3,0.193 7±0.021 8,与单纯照射组相比,其OD值均明显减少(P<0.01);h-R3联合照射组的A549细胞形态变化明显,存活细胞数明显少于单纯照射组。结论:尼妥珠单抗(h-R3)单独应用对A549细胞的生长增殖未见明显抑制作用,但增强了照射对A549细胞的生长抑制作用,其放射增敏的作用机制值得进行分子生物学水平的深入研究。 Objective: To investigate the effects ofNimotuzumab ( hR-3 ) combined with irradiation on pulmonary, adenocarcino ma A549 cells. Methods: Human pulmonary adenocarcinoma cells A549 was cultured in vitro for 48 h and was divided into 4 groups: control group, the irradiation group, h-R3 group, and h-R3 combined with radiation group. The h-R3 group were treated with h-R3 at different concentrations ( the final concentrations were 0.5, 5, 50, 100, and 1000 μg/mL) and then were cultured for 24 h. The irradia tion group received irradiation of 2, 4, 8. and 10 Gy X-ray by 6MV-X ray and then were cultured for 24 h. The combined group re ceived h-R3 at 50 jag/mL and were cultured for 24 h. followed by radiation at doses of 2, 4, 8, and 10 Gy and continuous culture of 24 h. MTT assay was used to evaluate the amount of survival cells. The characteristics of morphological changes were observed by inverted microscope. Results: The OD value ofA549 cells in the control group was 0.7867±0.0764. In the h-R3 group, the OD values of A549 cells treated with h-R3 at 0.5. 5. 50, 100, and 1000μg/mL were 0.7936 ± 0.0846, 0.8234 ± 0.0688.0.7603±0.0573, 0.7902 ± 0.0637, and 0.8208 ± 0.077. respectively. No significant difference was found in OD values between the control group and the h-R3 group ( P 〈 0.05 ). In the irradiation group, the OD Vaues of A549 cells treated with irradiation of 2.4, 8, and 10 Gy were 0.2460±0.0231, 0.3308 ± 0.0336, 0.3430± 0.0281, and 0.3175±0.0307, respectively, significantly lower than in thc control group ( P 〈 0.05 ). In the combined group, the OD values were 0.1923±0.0146, 0.2318±0.0206, 0.2930±0.0243, and 0.1937±0.0218, respectively, significantly lower than those in the irradiation group ( P 〈 0.01 ). In the combined group, obvious morphological changes were observed in A549 cells, and there were fewer viable cells than in the radiation group, with a statistical significance ( P 〈 0.05 ). Conclusion: Nimotuzumab ( hR-3 ) can increase the inhibitory effect of irradiation on human pulmonary adenocarcinoma A549 cells. Further study is warranted to elucidate the corresponding molecular mechanisms.
出处 《中国肿瘤临床》 CAS CSCD 北大核心 2011年第8期433-436,共4页 Chinese Journal of Clinical Oncology
基金 北京市科技计划基金(编号:D00802000290803)资助~~
关键词 尼妥珠单抗 肺腺癌细胞系A549 X射线 放射 甲基噻唑基四唑法 Nimotuzumab (h-R3): Lung adenocarcinoma A549 cells X ray Radiotherapy MTT
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参考文献13

  • 1Ho C.Cetuximab in locally advanced head-and-neck cancer:defining the population[J].Curr Oncol,2010,17 (4):48-51.
  • 2Boland W,Bebb G.The emerging role of nimotuzumab in the treatment of non-small cell lung cancer[J].Biologics,2010,4:289-298.
  • 3Jensen AD,Münter MW,Bischoff H,et al.Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab:the NEAR protocol (NCT00115518)[J].BMC Cancer,2006,6:122.
  • 4Crombet-Ramos T,Rak J,Perez R,et al.Antiproliferative,antiangiogenic and proapoptotic activity of h-R3:a humanized anti-EGFR antibody[J].Int J Cancer,2002,101(6):567-575.
  • 5Akashi Y,Okamoto I,Iwasa T,et al.Enhancement of the antitumor activity of ionising radiation by nimotuzumab,a humanized monoclonal antibody to the epidermal growth factor receptor,in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status[J].Br J Cancer,2008,98(4):749-755.
  • 6Raben D,Helfrich B,Chan DC,et al.The effects of cetuximab alone and in combination with radiation and/or chemotherapy in lung cancer[J].Clin Cancer Res,2005,11(2Pt 1):795-805.
  • 7曾斐,孙海,陈龙邦.西妥昔单抗对耐多西他赛肺腺癌细胞株放化疗敏感性的调变作用[J].中国肿瘤生物治疗杂志,2007,14(5):450-454. 被引量:7
  • 8Fakih M,Wong R.Efficacy of the monoclonal antibody EGFR inhibitors for the treatment of metastatic colorectal cancer[J].Curr Oncol,2010,17 Suppl 1:S3-S17.
  • 9Bjorkelund H,Gedda L,Andersson K.Comparing the epidermal growth factor interaction with four different cell lines:intriguing effects imply strong dependency of cellular context[J].PLoS ONE,2011,6 (1):1-7.
  • 10陈勇,刘巍.Cetuximab研究现状[J].中国肿瘤临床,2006,33(23):1376-1379. 被引量:4

二级参考文献36

  • 1Zhi-Zhong Liu,Wen-Ying Huang,Xiao-Sheng Li,Ju-Sheng Lin,Xiao-Kun Cai,Kuo-Huang Lian,He-Jun Zhou.Prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and micronucleus assay[J].World Journal of Gastroenterology,2005,11(44):7036-7039. 被引量:8
  • 2孙海,耿建,金洁,陈龙邦.人肺腺癌细胞系SPC-A1多西他赛耐药细胞系的建立及其特性[J].中国癌症杂志,2007,17(4):283-287. 被引量:6
  • 3Motzer RJ,Amato R,Todd M,et al.Phase Ⅱ trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma[J].Invest New Drugs,2003,21 (1):99101
  • 4Wu G,Barth RF,Yang W,et al.Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy[J].Bioconjug Chem,2004,15(1):185~194
  • 5Riemer AB,Kurz H,Klinger M,et al.Vaccination with cetuximab mimotopes and biological properties of induced anti-epidermal growth factor receptor antibodies[J].J Natl Cancer Inst,2005,97(22):1663~1670
  • 6Huether A,Hopfner M,Baradari V,et al.EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer[J].Biochem Pharmacol,2005,70(11):1568~1578
  • 7Huang SM,Bock JM,Harari PM.Epidermal growth factor receptor blockade with C225 modulates proliferation,apoptosis,and radiosensitivity in squamous cell carcinomas of the head and neck[J].Cancer Res,1999,59(8):1935~1940
  • 8Harding J,Burtness B.Cetuximab:an epidermal growth factor receptor chemeric hunan-murine monoclonal antibody[J].Drugs Today (Barc),2005,41(2):107~127
  • 9Sung FL,Poon TC,Hui EP,et al.Antitumor effect and enhancement of cytotoxic drug activity by cetuximab in nasopharyngeal carcinoma cells[J].In Vivo,2005,19(1):237~245
  • 10Rose WC,Wild R.Therapeutic synergy of oral taxane BMS-275183 and cetuximab versus human tumor xenografts[J].Clin Cancer Res,2004,10(21):7413~7417

共引文献11

同被引文献50

  • 1黄晓东,易俊林,高黎,徐国镇,金晶,杨伟志,卢泰祥,吴少雄,吴仁瑞,胡伟汉,谢伟长,韩非,高远红,高剑铭,潘建基,陈传本,朗锦义,李涛,董昱,付玉彬,樊林,李柏森,黎静,王晓怀,陈炳旭,高献书,张萍,吴湘玮,胡炳强.抗表皮生长因子受体单克隆抗体h—R3联合放疗治疗晚期鼻咽癌的Ⅱ期临床研究[J].中华肿瘤杂志,2007,29(3):197-201. 被引量:99
  • 2Bonner JA, Harari PM, GiraltJ, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck[J]. N Engl J Med, 2006, 354(6): 567-578.
  • 3Dassonville O, Bozec A, FischelJL, et al. EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences[J]. Crit Rev Oncol Hematol, 2007, 62(1): 53-61.
  • 4Bonner JA, Harari PM, GiraltJ, et al. Radiotherapy plus cetuximab for locoregionaUy advanced head and neck cancer: 5--year survival data from a phase 3 randomised trial, and relation between cetux- imab-induced rash and survival[J]. Lancet Oncol, 2010, 11(1): 21-28.
  • 5Baumann M, Krause M, Dikomey E, et al. EGFR-targeted an- ti-cancer drugs in radiotherapy: preclinical evaluation of mecha- nisms[J].Radiother Oncol, 2007, 83(3): 238-248.
  • 6Zips D, Krause M, Yaromina A, et al. Epidermal growth factor re- ceptor intfibitors for radiotherapy: biological rationale and preclini- cal results[J].J Pharm Pharmacol, 2008, 60(8): 1019-1028.
  • 7Williams JR, Zhang Y, Zhou H, et al. Genotype-dependent radio- sensitivity: clonogenic survival, apoptosis and cell-cycle redistribu- tion[J]. Int J Radiat Biol, 2008, 84(2): 151-164.
  • 8Kaushal N, Bansal MP. Inhibition of CDC2/Cyclin B1 in response to selenium-induced oxidative stress during spermatogenesis: po- tential role of Cdc25c and p21[J]. Mol Cell Biochem, 2007, 298 (1-2) :139-150.
  • 9GastaldoJ, Viau M, Bencokova Z, et al. Lead contamination results in late and slowly repairable DNA double-strand breaks and im- pacts upon the ATM-dependent signaling pathways[J].Toxicol Lett, 2007, 173(3): 201-214.
  • 10Short SC, Bourne S, Martindale C, et al. DNA damage responses at low radiation doses[J]. Radiat Res, 2005, 164(3): 292-302.

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