• 1.貴陽醫(yī)學院附屬醫(yī)院肛腸外科(貴州貴陽 550004);;
  • 2.貴州省人民醫(yī)院普通外科(貴州貴陽 550001);

目的  探討活體內人結直腸癌對5種化療藥物的敏感性。
方法  用9例結直腸癌患者的腫瘤組織建立結直腸癌裸鼠皮下移植瘤模型,分別應用5-氟尿嘧啶(5-FU)、奧沙利鉑(LOHP)、絲裂霉素(MMC)、阿霉素(ADM)及伊立替康(CPT-11)對移植瘤進行干預治療,觀察該5種藥物對裸鼠皮下移植瘤生長的影響。
結果  對照組裸鼠皮下移植瘤的體積明顯大于其余5個化療藥物組;6組裸鼠肝肺均無轉移。5種化療藥物對9例患者的裸鼠皮下移植瘤的最低和最高抑瘤率5-FU為23.6%和54.9%;LOHP為23.7%和69.5%;CPT-11為23.6%和82.6%;MMC為24.1%和48.1%;ADM為5.8%和20.7%。LOHP、CPT-11、5-FU和MMC組分別有7例、6例、4例和1例患者的裸鼠皮下移植瘤抑瘤率在40.0%以上。9例患者的移植瘤中,3種藥物抑瘤率均在40.0%以上者3例,2種藥物抑瘤率均在40.0%以上者4例,1例除CPT-11的抑瘤率為82.6%外,其余4種藥物的抑瘤率均在30.0%以下,1例5種化療藥物的抑瘤率均在31.0%以下。5個化療藥物組抑瘤率之間的差異具有統(tǒng)計學意義(H=24.061 2,P=0.000 1),其中,與ADM組相比,5-FU組、MMC組、LOHP組及CPT-11組的抑瘤率較高(P<0.05),后4組之間抑瘤率的差異均無統(tǒng)計學意義(P>0.05)。
結論  同一結直腸癌患者的裸鼠皮下移植瘤對不同化療藥物的敏感性存在較大差異,同一種化療藥物對不同結直腸癌患者的裸鼠皮下移植瘤的抑瘤率也存在較大差異。在5種化療藥物中,LOHP和CPT-11對裸鼠皮下結直腸癌移植瘤的抑瘤率最高,其次為5-FU和MMC。

引用本文: 甄運寰,顏登國,張東興,李國勝,龔慧. 人結直腸癌化療藥物的裸鼠體內敏感性實驗△. 中國普外基礎與臨床雜志, 2013, 20(1): 48-53. doi: 復制

1. Underhill C, Goldstein D, Gorbounova VA, et al. A randomized phaseⅡtrial of pemetrexed plus irinotecan (ALIRI) versus leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of locally advanced or metastatic colorectal cancer[J]. Oncology, 2007, 73(1-2):9-20.
2. Scalamogna R, Brugnatelli S, Tinelli C, et al. UFT as maintenance therapy in patients with advanced colorectal cancer responsive to the FOLFOX4 regimen[J]. Oncology, 2007, 72(5-6):267-273.
3. Satram-Hoang S, Lee L, Yu S, et al. Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer[J]. J Gastrointest Cancer, 2012, [Epub ahead of print].
4. Mccleary NJ, Odejide O, Szymonifka J, et al. Safety and effecti-veness of oxaliplatin-based chemotherapy regimens in adults 75 years and older with colorectal cancer[J]. Clin Colorectal Cancer,2012, [Epub ahead of print].
5. Focan C, Kreutz F, Graas MP, et al. Phase Ⅰ-Ⅱ study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid, carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study[J]. Pathol Biol (Paris), 2012, [Epub ahead of print].
6. 張洪偉, 同李平, 孫力. 結直腸癌的個體化治療進展[J]. 中國普外基礎與臨床雜志, 2009, 16(9):689-692.
7. Rayson D, Urquhart R, Cox M, et al. Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in a Canadian province:a population-based analysis[J]. J Oncol Pract, 2012, 8(4):253-259.
8. Oyan B. Why do targeted agents not work in the adjuvant settingin colon cancer?[J] . Expert Rev Anticancer Ther, 2012, 12(10):1337-1345.
9. Tohyama N, Tanaka S, Onda K, et al. Influence of anticancer agents on cell survival, proliferation, and CD4+CD25+Foxp3+ regulatory T cell-frequency in human peripheral-blood mononuclear cells activated by T cell-mitogen[J]. Int Immunopharmacol,2012, [Epub ahead of print].
10. Adachi W, Sugenoya A, Horigome N, et al. The antitumor activityand immunosuppressive effects of 5-fluorouracil suppositories in rectal cancer patients[J]. Surg Today, 1992, 22(3):221-225.
11. Maeda K, Hazama S, Tokuno K, et al. Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity[J]. Anticancer Res, 2011, 31(12):4569-4574.
12. 張東興, 顏登國, 趙丙波. 人大腸癌裸鼠皮下移植瘤模型的建立[J]. 貴陽醫(yī)學院學報, 2010, 35(3):247-250.
13. 韓杰, 檀碧波, 呂炳蓉, 等. 胃癌與大腸癌原代細胞培養(yǎng)化療藥物敏感性的對比[J]. 中華普通外科雜志, 2008, 23(6):464-465.
14. 馬望, 王留興, 王瑞林, 等. 胰島素增強5-氟尿嘧啶對體外結腸癌細胞的細胞毒作用[J]. 中華腫瘤雜志, 2010, 32(3):169-172.
15. 周進明, 鐘大平, 周琪, 等. 地塞米松影響結腸癌細胞對奧沙利鉑和氟尿嘧啶化療敏感性的實驗研究[J]. 中國腫瘤臨床, 2010, 37(3):142-145.
16. 姚祺, 李太原. 大腸癌細胞體外培養(yǎng)藥敏試驗與臨床特征關系探討[J]. 實用癌癥雜志, 2006, 21(6):564-566.
17. Kim JH, Kim HS, Choi DR, et al. A phaseⅡstudy of mitomycin-C and S-1 as third-line chemotherapy in patients with advanced colorectal cancer[J]. Oncol Lett, 2011, 2(6):1253-1256.
18. Voigt W, Behrmann C, Schlueter A, et al. A new chemoemboliz-ation protocol in refractory liver metastasis of colorectal cancer—a feasibility study[J]. Onkologie, 2002, 25(2):158-164.
19. Ducreux M, Raoul JL, Marti P, et al. High-dose irinotecan plus LV5FU2 or simplified LV5FU (HD-FOLFIRI) for patients withuntreated metastatic colorectal cancer:a new way to allow resection of liver metastases?[J]. Oncology, 2008, 74(1-2):17-24.
20. Yu DS, Li Y, Huang XE, et al. Effect of portal vein chemotherapy on liver metastasis after surgical resection of colorectal cancer[J]. Asian Pac J Cancer Prev, 2012, 13(9):4699-4701.
21. Ono T, Ishida H, Kumamoto K, et al. Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-based chemotherapy[J]. Oncol Lett, 2012, 4(5):905-909.
22. Kataoka K, Kanazawa A, Nakajima A, et al. The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM):a single-centered retrospective study[J]. Surg Today, 2012, [Epub ahead of print].
23. Deboever G, Hiltrop N, Cool M, et al. Alternative treatment opti-ons in colorectal cancer patients with 5-Fluorouracil-or capecitabine-induced cardiotoxicity[J]. Clin Colorectal Cancer, 2012, [Epub ahead of print].
24. Mishra J, Drummond J, Quazi SH, et al. Prospective of colon can-cer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis[J]. Crit Rev Oncol Hematol, 2012, [Epub ahead of print].
25. Mishima H, Ikenaga M, Yasui M. Safety and efficacy of FOLFOX and FOLFIRI in elderly patients with colorectal cancer[J]. Nihon Rinsho, 2011, 69 Suppl 3:554-558.
26. Kline CL, Sheikh HS, Scicchitano A, et al. Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients[J]. Cancer Biol Ther, 2011, 12(7):557-568.
27. de Melo JV, Vieira de Melo MS, Abad MH. Clinical and radiological response with FOLFOXIRI and bevacizumab as third-line therapy after mFOLFOX6 and FOLFIRI failure[J]. Anticancer Drugs, 2011, 22 Suppl 2:S19-S20.
  1. 1. Underhill C, Goldstein D, Gorbounova VA, et al. A randomized phaseⅡtrial of pemetrexed plus irinotecan (ALIRI) versus leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of locally advanced or metastatic colorectal cancer[J]. Oncology, 2007, 73(1-2):9-20.
  2. 2. Scalamogna R, Brugnatelli S, Tinelli C, et al. UFT as maintenance therapy in patients with advanced colorectal cancer responsive to the FOLFOX4 regimen[J]. Oncology, 2007, 72(5-6):267-273.
  3. 3. Satram-Hoang S, Lee L, Yu S, et al. Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer[J]. J Gastrointest Cancer, 2012, [Epub ahead of print].
  4. 4. Mccleary NJ, Odejide O, Szymonifka J, et al. Safety and effecti-veness of oxaliplatin-based chemotherapy regimens in adults 75 years and older with colorectal cancer[J]. Clin Colorectal Cancer,2012, [Epub ahead of print].
  5. 5. Focan C, Kreutz F, Graas MP, et al. Phase Ⅰ-Ⅱ study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid, carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study[J]. Pathol Biol (Paris), 2012, [Epub ahead of print].
  6. 6. 張洪偉, 同李平, 孫力. 結直腸癌的個體化治療進展[J]. 中國普外基礎與臨床雜志, 2009, 16(9):689-692.
  7. 7. Rayson D, Urquhart R, Cox M, et al. Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in a Canadian province:a population-based analysis[J]. J Oncol Pract, 2012, 8(4):253-259.
  8. 8. Oyan B. Why do targeted agents not work in the adjuvant settingin colon cancer?[J] . Expert Rev Anticancer Ther, 2012, 12(10):1337-1345.
  9. 9. Tohyama N, Tanaka S, Onda K, et al. Influence of anticancer agents on cell survival, proliferation, and CD4+CD25+Foxp3+ regulatory T cell-frequency in human peripheral-blood mononuclear cells activated by T cell-mitogen[J]. Int Immunopharmacol,2012, [Epub ahead of print].
  10. 10. Adachi W, Sugenoya A, Horigome N, et al. The antitumor activityand immunosuppressive effects of 5-fluorouracil suppositories in rectal cancer patients[J]. Surg Today, 1992, 22(3):221-225.
  11. 11. Maeda K, Hazama S, Tokuno K, et al. Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity[J]. Anticancer Res, 2011, 31(12):4569-4574.
  12. 12. 張東興, 顏登國, 趙丙波. 人大腸癌裸鼠皮下移植瘤模型的建立[J]. 貴陽醫(yī)學院學報, 2010, 35(3):247-250.
  13. 13. 韓杰, 檀碧波, 呂炳蓉, 等. 胃癌與大腸癌原代細胞培養(yǎng)化療藥物敏感性的對比[J]. 中華普通外科雜志, 2008, 23(6):464-465.
  14. 14. 馬望, 王留興, 王瑞林, 等. 胰島素增強5-氟尿嘧啶對體外結腸癌細胞的細胞毒作用[J]. 中華腫瘤雜志, 2010, 32(3):169-172.
  15. 15. 周進明, 鐘大平, 周琪, 等. 地塞米松影響結腸癌細胞對奧沙利鉑和氟尿嘧啶化療敏感性的實驗研究[J]. 中國腫瘤臨床, 2010, 37(3):142-145.
  16. 16. 姚祺, 李太原. 大腸癌細胞體外培養(yǎng)藥敏試驗與臨床特征關系探討[J]. 實用癌癥雜志, 2006, 21(6):564-566.
  17. 17. Kim JH, Kim HS, Choi DR, et al. A phaseⅡstudy of mitomycin-C and S-1 as third-line chemotherapy in patients with advanced colorectal cancer[J]. Oncol Lett, 2011, 2(6):1253-1256.
  18. 18. Voigt W, Behrmann C, Schlueter A, et al. A new chemoemboliz-ation protocol in refractory liver metastasis of colorectal cancer—a feasibility study[J]. Onkologie, 2002, 25(2):158-164.
  19. 19. Ducreux M, Raoul JL, Marti P, et al. High-dose irinotecan plus LV5FU2 or simplified LV5FU (HD-FOLFIRI) for patients withuntreated metastatic colorectal cancer:a new way to allow resection of liver metastases?[J]. Oncology, 2008, 74(1-2):17-24.
  20. 20. Yu DS, Li Y, Huang XE, et al. Effect of portal vein chemotherapy on liver metastasis after surgical resection of colorectal cancer[J]. Asian Pac J Cancer Prev, 2012, 13(9):4699-4701.
  21. 21. Ono T, Ishida H, Kumamoto K, et al. Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-based chemotherapy[J]. Oncol Lett, 2012, 4(5):905-909.
  22. 22. Kataoka K, Kanazawa A, Nakajima A, et al. The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM):a single-centered retrospective study[J]. Surg Today, 2012, [Epub ahead of print].
  23. 23. Deboever G, Hiltrop N, Cool M, et al. Alternative treatment opti-ons in colorectal cancer patients with 5-Fluorouracil-or capecitabine-induced cardiotoxicity[J]. Clin Colorectal Cancer, 2012, [Epub ahead of print].
  24. 24. Mishra J, Drummond J, Quazi SH, et al. Prospective of colon can-cer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis[J]. Crit Rev Oncol Hematol, 2012, [Epub ahead of print].
  25. 25. Mishima H, Ikenaga M, Yasui M. Safety and efficacy of FOLFOX and FOLFIRI in elderly patients with colorectal cancer[J]. Nihon Rinsho, 2011, 69 Suppl 3:554-558.
  26. 26. Kline CL, Sheikh HS, Scicchitano A, et al. Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients[J]. Cancer Biol Ther, 2011, 12(7):557-568.
  27. 27. de Melo JV, Vieira de Melo MS, Abad MH. Clinical and radiological response with FOLFOXIRI and bevacizumab as third-line therapy after mFOLFOX6 and FOLFIRI failure[J]. Anticancer Drugs, 2011, 22 Suppl 2:S19-S20.