• 杭州市第一人民醫(yī)院呼吸內(nèi)科( 浙江杭州 310006)通訊作者: 任振義, E-mail: huxike123@ yahoo. com. cn;

目的  探討患者體內(nèi)肺癌細(xì)胞Ku80 蛋白含量與其對(duì)順鉑敏感性的相關(guān)性。方法  收集肺癌患者胸腔積液中的肺癌細(xì)胞進(jìn)行體外原代培養(yǎng), 通過(guò)傳代進(jìn)行純化和擴(kuò)增后進(jìn)行實(shí)驗(yàn)。體外藥敏試驗(yàn)采用CCK-8 法測(cè)定肺癌細(xì)胞對(duì)順鉑的敏感性, 獲得各樣本的半數(shù)抑制濃度( IC50 ) 。利用Western blot 法測(cè)定各樣本細(xì)胞內(nèi)Ku80 蛋白含量。分析Ku80 蛋白含量與順鉑敏感性的相關(guān)性。結(jié)果  非小細(xì)胞肺癌( NSCLC) 組IC50 為( 4. 40 ±3. 39) mg/L, 小細(xì)胞肺癌( SCLC) 組IC50 為( 1. 02 ±0. 54) mg/L, 二者比較差異有統(tǒng)計(jì)學(xué)意義( P  lt;0. 001) 。NSCLC 組Ku80 蛋白相對(duì)含量為0. 80 ±0. 45,而SCLC 組為0. 48 ±0. 25, 二組之間比較差異有統(tǒng)計(jì)學(xué)意義( P  lt;0. 05) 。通過(guò)相關(guān)性分析得到肺癌患者Ku80 含量與IC50呈正相關(guān)( r = 0. 618, P  lt; 0. 001) 。結(jié)論  NSCLC 患者Ku80 基因表達(dá)高于SCLC患者, 可能與NSCLC 對(duì)化療敏感性差有關(guān)。肺癌細(xì)胞Ku80 蛋白含量與其對(duì)順鉑敏感性呈負(fù)相關(guān)。Ku80 蛋白含量可作為預(yù)測(cè)肺癌患者以鉑類(lèi)為基礎(chǔ)的化療敏感性的候選指標(biāo)

引用本文： 任振義,葉盛,葉健,王利民. 人體內(nèi)肺癌細(xì)胞Ku80 蛋白含量與順鉑化療敏感性的關(guān)系研究. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(6): 631-634. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)呼吸與危重監(jiān)護(hù)雜志》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

1. Cho BC, Kim JH, Soo RA, et al. The role of monoclonal antibody in combination with first-line chemotherapy in Asian patients with advanced non-small cell lung cancer. Yonsei Med J, 2010, 51: 1-8 .
2. Yang CT, Hung JY, Lai CL, et al. Gefitinib as first-line therapy for advanced or metastatic non-small cell lung cancer patients in southern Taiwan. Kaohsiung J Med Sci, 2010, 26: 1-7.
3. Demedts IK, Vermaelen KY, van Meerbeeck JP. Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J, 2010, 35: 202 -215.
4. Shao CJ, Fu J, Shi HL, et al. Activities of DNA-PK and Ku86, but not Ku70, may predict sensitivity to cisplatin in human gliomas. J Neurooncol, 2008 , 89: 27-35.
5. 任振義, 金一尊. Ku 蛋白在腫瘤發(fā)生中的作用及其靶向抑制策略. 國(guó)際放射醫(yī)學(xué)核醫(yī)學(xué)雜志, 2008, 32: 305-307.
6. Komuro Y, Watanabe T, Hosoi Y, et al. The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer, 2002, 95: 1199-1205.
7. Tseng RC, Hsieh FJ, Shih CM, et al. Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous endjoining pathway genes: a multiple genotype-phenotype study.Cancer, 2009 , 115: 2939-2948.
8. Kuribayashi T, Ohara M, Sora S, et al. Scriptaid, a novel histone deacetylase inhibitor, enhances the response of human tumor cells to radiation. Int J Mol Med, 2010, 25: 25-29.
9. 熊建文, 肖化, 張鎮(zhèn)西. MTT 法和CCK-8 法檢測(cè)細(xì)胞活性之測(cè)試條件比較. 激光生物學(xué)報(bào), 2007, 16: 559 -562.
10. 唐夢(mèng)琳, 鄧萬(wàn)明. 肺癌順鉑耐藥的分子機(jī)制研究進(jìn)展. 華西醫(yī)學(xué), 2009, 24: 238-240 .
11. 方美玉. 進(jìn)展期非小細(xì)胞肺癌治療進(jìn)展. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2008 , 7: 481-484 .
12. 金兒, 任振義, 盧忠, 等. X 線照射后A549 肺癌細(xì)胞Ku80 mRNA 及其蛋白表達(dá)的變化. 中華放射醫(yī)學(xué)與防護(hù)雜志, 2009, 29: 393 -395.
13. Sibanda BL, Chirgadze DY, Blundell TL. Crystal structure of DNAPKcs reveals a large open-ring cradle comprised of HEAT repeats.Nature, 2010, 463 : 118-121.
14. Deriano L, Stracker TH, Baker A, et al. Roles for NBS1 in alternative nonhomologous end-joining of V ( D) J recombination intermediates.Mol Cell, 2009, 34 : 13-25.
15. 韓國(guó)棟, 王遠(yuǎn)東, 袁進(jìn), 等. 體外腫瘤藥敏試驗(yàn)指導(dǎo)非小細(xì)胞肺癌個(gè)體戶新輔助化療的臨床研究. 內(nèi)科, 2008 , 3: 493-496 .
16. Xing J, Wu X, Vaporciyan AA, et al. Prognostic significance of ataxia- telangiectasia mutated, DNA-dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86-kD subunit expression in patients with non-small cell lung cancer.Cancer, 2008 , 112: 2756-2764.
17. Liu B, Wang T, Qian X, et al. Anticancer effect of tetrandrine on primary cancer cells isolated fromascites and pleural fluids. Cancer Lett, 2008, 268: 166-175.
  1. 1. Cho BC, Kim JH, Soo RA, et al. The role of monoclonal antibody in combination with first-line chemotherapy in Asian patients with advanced non-small cell lung cancer. Yonsei Med J, 2010, 51: 1-8 .
  2. 2. Yang CT, Hung JY, Lai CL, et al. Gefitinib as first-line therapy for advanced or metastatic non-small cell lung cancer patients in southern Taiwan. Kaohsiung J Med Sci, 2010, 26: 1-7.
  3. 3. Demedts IK, Vermaelen KY, van Meerbeeck JP. Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J, 2010, 35: 202 -215.
  4. 4. Shao CJ, Fu J, Shi HL, et al. Activities of DNA-PK and Ku86, but not Ku70, may predict sensitivity to cisplatin in human gliomas. J Neurooncol, 2008 , 89: 27-35.
  5. 5. 任振義, 金一尊. Ku 蛋白在腫瘤發(fā)生中的作用及其靶向抑制策略. 國(guó)際放射醫(yī)學(xué)核醫(yī)學(xué)雜志, 2008, 32: 305-307.
  6. 6. Komuro Y, Watanabe T, Hosoi Y, et al. The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer, 2002, 95: 1199-1205.
  7. 7. Tseng RC, Hsieh FJ, Shih CM, et al. Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous endjoining pathway genes: a multiple genotype-phenotype study.Cancer, 2009 , 115: 2939-2948.
  8. 8. Kuribayashi T, Ohara M, Sora S, et al. Scriptaid, a novel histone deacetylase inhibitor, enhances the response of human tumor cells to radiation. Int J Mol Med, 2010, 25: 25-29.
  9. 9. 熊建文, 肖化, 張鎮(zhèn)西. MTT 法和CCK-8 法檢測(cè)細(xì)胞活性之測(cè)試條件比較. 激光生物學(xué)報(bào), 2007, 16: 559 -562.
  10. 10. 唐夢(mèng)琳, 鄧萬(wàn)明. 肺癌順鉑耐藥的分子機(jī)制研究進(jìn)展. 華西醫(yī)學(xué), 2009, 24: 238-240 .
  11. 11. 方美玉. 進(jìn)展期非小細(xì)胞肺癌治療進(jìn)展. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2008 , 7: 481-484 .
  12. 12. 金兒, 任振義, 盧忠, 等. X 線照射后A549 肺癌細(xì)胞Ku80 mRNA 及其蛋白表達(dá)的變化. 中華放射醫(yī)學(xué)與防護(hù)雜志, 2009, 29: 393 -395.
  13. 13. Sibanda BL, Chirgadze DY, Blundell TL. Crystal structure of DNAPKcs reveals a large open-ring cradle comprised of HEAT repeats.Nature, 2010, 463 : 118-121.
  14. 14. Deriano L, Stracker TH, Baker A, et al. Roles for NBS1 in alternative nonhomologous end-joining of V ( D) J recombination intermediates.Mol Cell, 2009, 34 : 13-25.
  15. 15. 韓國(guó)棟, 王遠(yuǎn)東, 袁進(jìn), 等. 體外腫瘤藥敏試驗(yàn)指導(dǎo)非小細(xì)胞肺癌個(gè)體戶新輔助化療的臨床研究. 內(nèi)科, 2008 , 3: 493-496 .
  16. 16. Xing J, Wu X, Vaporciyan AA, et al. Prognostic significance of ataxia- telangiectasia mutated, DNA-dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86-kD subunit expression in patients with non-small cell lung cancer.Cancer, 2008 , 112: 2756-2764.
  17. 17. Liu B, Wang T, Qian X, et al. Anticancer effect of tetrandrine on primary cancer cells isolated fromascites and pleural fluids. Cancer Lett, 2008, 268: 166-175.