內皮抑素聯合化學療法治療腫瘤進展后二線使用協同抗腫瘤作用研究_《華西醫學》

作者：

張煒 , 伍璐 , 王資 , 劉燕楊 ,  羅鋒

四川大學華西醫院腫瘤中心（成都，610041）;

關鍵詞：

內皮抑素腫瘤進展化學療法協同作用

DOI：

10.7507/1002-0179.20130308

視頻：

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目的　建立重組人內皮抑素（恩度）聯合順鉑一線治療腫瘤進展的小鼠模型，繼續應用內皮抑素聯合紫杉醇二線治療，研究內皮抑素協同紫杉醇抗腫瘤的作用及其機制。方法　建立小鼠Lewis 肺癌移植瘤動物模型，內皮抑素聯合順鉑治療后觀察腫瘤生長情況，遴選出腫瘤進展小鼠16只，隨機留取1只，余15只小鼠隨機分成紫杉醇組和聯合用藥組治療，觀察療效。另取上述腫瘤進展小鼠1只，剝離腫瘤組織，重新接種，將成瘤小鼠隨機分成生理鹽水組，紫杉醇組及聯合用藥組治療，觀察療效。治療結束后24 h處死所有小鼠，采用免疫組織化學CD31單克隆抗體標記檢測微血管密度（MVD），采用原位末端轉移酶（TUNEL）檢測細胞凋亡。結果　只腫瘤進展小鼠中，聯合用藥組相比紫杉醇組生存時間無明顯延長，但腫瘤體積增長較慢；而在重新接種成瘤的小鼠中，聯合用藥組較其余各組微血管密度明顯減低（P＜0.05），凋亡指數明顯增加（P＜0.05），腫瘤體積抑制明顯。結論　在內皮抑素聯合順鉑治療腫瘤進展的小鼠模型中，繼續應用內皮抑素治療與紫杉醇有較明顯的協同抗腫瘤作用。

引用本文： 張煒,伍璐,王資,劉燕楊,羅鋒. 內皮抑素聯合化學療法治療腫瘤進展后二線使用協同抗腫瘤作用研究. 華西醫學, 2013, 28(7): 989-993. doi: 10.7507/1002-0179.20130308 復制

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12.	Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease[J]. Nat Med, 1995, 1(1): 27-31.
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14.	Skovseth DK, Veuger MJ, Haraldsen G, et al. Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis, and perivascular cell recruitment in vivo[J]. Blood, 2005,105(3): 1044-1051.
15.	Wang HL, Ning T, Luo F, et al. Effect of endostatin on preventing postoperative progression of distant metastasis in a murine lung cancer model[J]. Tumori, 2011, 97(6): 787-793.
16.	Saarela J, Ylikärppä R, Rehn M, et al. Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific diffences in the expression of the corresponding transcript[J]. Matrix Biol, 1998, 16(6): 319-328.

1. 　Junttila MR, Karnezis AN, Garcia D, et al. Selective activation of p53-mediated tumor suppression in high-grade tumors[J]. Nature, 2010, 468(7323): 567-571.
2. 　Folkman J. Role of angiogenesis in tumor growth and metastasis[J]. Semin Oncol, 2002, 29(6 Suppl 16): 15-18.
3. 　Ning T, Yan X, Lu ZJ, et al. Gene therapy with the angiogenesis inhibitor endostatin in an orthotopic lung cancer murine model[J]. Hum Gene Ther, 2009, 20(2): 103-111.
4. 　Ma J, Waxman DJ. Combination of anti-angiogenesis with chemotherapy for more effective cancer treatment[J]. Molecular Cancer Therapeutics, 2008, 7(12): 3670-3684.
5. 　O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth[J]. Cell, 1997, 88(2): 277-285.
6. 　Cao Y. Endogenous angiogenesis inbibitors and their therapeutic implications[J]. Int J Biochem Cell Biol, 2001, 33 (4): 357-369.
7. 　Boehm T, Folkman J, Browder T, et al. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance[J]. Nature, 1997, 390(6658): 404-407.
8. 　黎培員, 馮作化, 張桂梅, 等.化療聯合重組Endostatin對小鼠種植瘤的治療作用[J].中國腫瘤生物治療雜志, 2002, 9(1): 43-47.
9. 　Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomized phase 3 trial[J]. Lancet Oncol, 2013, 14(1): 29-37.
10. 　Huang G, Chen L. Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma[J]. J Cancer Res Clin Oncol, 2010, 136(8): 1201-1211.
11. 　Weidner N, Semple JP, Folkman J, et al.Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma[J]. N Engl J Med, 1991, 324(1): 1-8.
12. 　Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease[J]. Nat Med, 1995, 1(1): 27-31.
13. 　Dhanabal M, Ramchandran R, Waterman MJ, et al. Endostatin induces endothelial cell apoptosis[J]. J Biol Chem, 1999, 274(17): 11721-11726.
14. 　Skovseth DK, Veuger MJ, Haraldsen G, et al. Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis, and perivascular cell recruitment in vivo[J]. Blood, 2005,105(3): 1044-1051.
15. 　Wang HL, Ning T, Luo F, et al. Effect of endostatin on preventing postoperative progression of distant metastasis in a murine lung cancer model[J]. Tumori, 2011, 97(6): 787-793.
16. 　Saarela J, Ylikärppä R, Rehn M, et al. Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific diffences in the expression of the corresponding transcript[J]. Matrix Biol, 1998, 16(6): 319-328.

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內皮抑素聯合化學療法治療腫瘤進展后二線使用協同抗腫瘤作用研究

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