• 川北醫(yī)學(xué)院附屬醫(yī)院普外科（四川南充 637000）;

目的 建立人胃癌羥喜樹堿（HCPT）耐藥細(xì)胞系SGC-7901/HCPT裸鼠皮下移植瘤模型并研究其生物學(xué)特征。方法 體外培養(yǎng)人胃癌細(xì)胞系SGC-7901和SGC-7901/HCPT，采用皮下注射方式分別接種至裸小鼠，待腫瘤長徑達(dá)1.0 cm時，將其切下剪成直徑為0.1～0.2 cm小塊，再接種至第2代裸鼠皮下進(jìn)行傳代，重復(fù)至第4代。對第4代移植瘤光鏡下的組織學(xué)形態(tài)、電鏡下的超微結(jié)構(gòu)及生長特點(diǎn)進(jìn)行觀察，四甲基偶氮唑鹽（MTT）法檢測其耐藥性。結(jié)果 裸鼠皮下移植瘤呈圓形或橢圓形，表面可見豐富的血管網(wǎng)。光鏡下見親代細(xì)胞移植瘤的細(xì)胞大小基本一致，排列較整齊，細(xì)胞核的大小較一致； 而耐藥細(xì)胞移植瘤的細(xì)胞形態(tài)較不規(guī)則，排列紊亂，細(xì)胞核的大小差異較大。電鏡下見親代細(xì)胞移植瘤細(xì)胞的細(xì)胞核無腫脹，線粒體及內(nèi)質(zhì)網(wǎng)基本正常； 耐藥細(xì)胞移植瘤細(xì)胞的細(xì)胞核略腫脹，核異染色質(zhì)凝集，線粒體及內(nèi)質(zhì)網(wǎng)腫脹較明顯。與親代細(xì)胞第4代移植瘤相比較，耐藥細(xì)胞第4代移植瘤對HCPT的耐藥指數(shù)為9.02±0.78，對阿霉素、絲裂霉素C、5-氟尿嘧啶及依托泊苷的耐藥指數(shù)分別為1.24±0.09、1.31±0.17、0.96±0.12和1.07±0.16。結(jié)論 本實(shí)驗(yàn)建立了穩(wěn)定的人胃癌HCPT耐藥細(xì)胞系SGC-7901/HCPT裸鼠移植瘤模型，耐藥細(xì)胞對HCPT的耐藥性保持穩(wěn)定，且對其他化療藥物無交叉耐藥性，可用于下游實(shí)驗(yàn)研究。

引用本文： 王攀,魏壽江,何一,侯華芳,王崇樹. 人胃癌SGC-7901/HCPT裸鼠移植瘤的建立及生物學(xué)特性研究. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(11): 1147-1151. doi: 復(fù)制

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14. Rygaard J, Povlsen CO. Hetero transplantation of a human malignant tumor to nude mice [J]. Act Path Microbiol Scand, 1969; 77(4): 758-760.
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19. 萬繼英, 韓庶勇. 腫瘤實(shí)驗(yàn)動物模型的建立及應(yīng)用研究進(jìn)展 [J]. 醫(yī)學(xué)綜述， 2009; 15(19): 2959-2961.
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23. Kelland LR. Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development [J]. Eur J Cancer, 2004; 40(6): 827-836.
24. Prenen H, Deroose C, Vermaelen P, et al. Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography [J]. Anticancer Res, 2006; 26(2A): 1247-1252.
25. Zhang YH, Wu Q, Xiao XY, et al. Silencing MRP4 by small interfering RNA reverses acquired DDP resistance of gastric cancer cell [J]. Cancer Lett, 2010; 291(1): 76-82.
26. Hawkins LK, Lemoine NR, Kirn D. Oncolytic biotherapy: a novel therapeutic plafform [J]. Lancet Oncol, 2002; 3(1): 17-26.
  1. 1. Meyer HJ. The influence of case load and the extent of resection on the quality of treatment outcome in gastric cancer [J]. Eur J Surg Oncol, 2005; 31(6): 595-604.
  2. 2. Sivins A, Pedrazzani C, Roviello F, et al. Surgical treatment of gastric cancer in Latvia: results of centralized experience [J]. Eur J Surg Oncol, 2009; 35(5): 481-485.
  3. 3. Morabito A, Carillio G, Longo R. Systemic treatment of gastric cancer [J]. Crit Rev Oncol Hematol, 2009; 70(3): 216-234.
  4. 4. Cervenak J, Andrikovics H, Ozvegy-Laczka C, et al. The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology [J]. Cancer Lett, 2006; 234(1): 62-72.
  5. 5. Chun JH, Kim HK, Lee JS, et al. Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy [J]. Jpn J Clin Oncol, 2004; 34(1): 8-13.
  6. 6. 林蕓秀, 呂聯(lián)煌, 林錦娟, 等. 人小細(xì)胞肺癌NCI-H446細(xì)胞裸鼠異種移植瘤模型的建立 [J]. 實(shí)驗(yàn)動物科學(xué)與管理, 2004; 21(3): 1-3.
  7. 7. 何一, 王崇樹, 魏壽江, 等. 人胃癌耐羥基喜樹堿細(xì)胞株SGC-7901/HCPT 的建立及其生物學(xué)性狀 [J]. 中國現(xiàn)代醫(yī)生, 2008; 46(3): 15-17.
  8. 8. Branimir IS. Natural and Acquired Resistance to Cancer Therapies [A]. In: John Mendelsohn MD, Peter M. Howley MD, Mark A. Israel MD, et al. The Molecular Basis of Cancer [M]. Third Ed, 2008: 583-592.
  9. 9. Morgillo F, Bareschino MA, Bianco R, et al. Primary and acquired resistance to anti-EGFR targeted drugs in cancer therapy [J]. Differentiation, 2007; 75(9): 788-799.
  10. 10. Duesberg P, Li R, Sachs R, et al. Cancer drug resistance: the central role of the karyotype [J]. Drug Resist Updat, 2007; 10(1-2): 51-58.
  11. 11. Ozben T. Mechanisms and strategies to overcome multiple drug resistance in cancer [J]. FEBS Lett, 2006; 580(12): 2903-2909.
  12. 12. Jabr-Milane LS, van Vlerken LE, Yadav S, et al. Multi-functional nanocarriers to overcome tumor drug resistance [J]. Cancer Treat Rev, 2008; 34(7): 592-602.
  13. 13. McConkey DJ, Zhu K. Mechanisms of proteasome inhibitor action and resistance in cancer [J]. Drug Resist Updat, 2008; 11(4-5): 164-179.
  14. 14. Rygaard J, Povlsen CO. Hetero transplantation of a human malignant tumor to nude mice [J]. Act Path Microbiol Scand, 1969; 77(4): 758-760.
  15. 15. 劉孟剛, 楊俊濤, 劉宏鳴, 等. GA反義基因?qū)β闶笪赴┮浦擦黾?xì)胞凋亡的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(1): 4-7.
  16. 16. 黃喆, 郭克建, 何三光. 柳氮磺胺吡啶和5-氟尿嘧啶對裸鼠皮下移植瘤胰腺癌細(xì)胞BxPC-3凋亡基因的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(8): 550-555.
  17. 17. Mickisch GH, Garin A, van Poppel H, et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial [J]. Lancet, 2001; 358(9286): 966-970.
  18. 18. Metzinger DS, Taylor DD, Gercel-Taylor C. Induction of p53 and drug resistance following treatment with cisplatin or paclitaxel in ovarian cancer cell lines [J]. Cancer Lett, 2006; 236(2): 302-308.
  19. 19. 萬繼英, 韓庶勇. 腫瘤實(shí)驗(yàn)動物模型的建立及應(yīng)用研究進(jìn)展 [J]. 醫(yī)學(xué)綜述， 2009; 15(19): 2959-2961.
  20. 20. Yoshiba S, Ito D, Nagumo T, et al. Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G(1) phase cell cycle arrest [J]. Oral Oncol, 2009; 45(2): 109-115.
  21. 21. 梁永鉅， 符立梧， 馮海林, 等. KBv200裸鼠移植瘤模型的建立及其耐藥特性的探討 [J] . 中國藥理學(xué)通報, 2000; 16(6)： 705-707.
  22. 22. Henss H, Fiebig HH, Meinhardt K, et al. Clonal growth of human tumor xenografts. First experiences in drug testing [J]. J Cancer Res Clin Oncol, 1984; 108(2): 233-235.
  23. 23. Kelland LR. Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development [J]. Eur J Cancer, 2004; 40(6): 827-836.
  24. 24. Prenen H, Deroose C, Vermaelen P, et al. Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography [J]. Anticancer Res, 2006; 26(2A): 1247-1252.
  25. 25. Zhang YH, Wu Q, Xiao XY, et al. Silencing MRP4 by small interfering RNA reverses acquired DDP resistance of gastric cancer cell [J]. Cancer Lett, 2010; 291(1): 76-82.
  26. 26. Hawkins LK, Lemoine NR, Kirn D. Oncolytic biotherapy: a novel therapeutic plafform [J]. Lancet Oncol, 2002; 3(1): 17-26.