談蘊璞 1 , 李剛 2 , 吳小劍 1 , 何小文 1 , 柯嘉 1 , 張晶 2 , 蘭平 1
  • 1. 中山大學附屬第六醫(yī)院結直腸外科(廣東廣州 510655);;
  • 2. 香港理工大學紡織與織衣系(香港);

目的  研究擔載抗腫瘤藥物5-氟尿嘧啶(5-FU)的左旋聚乳酸(PLLA)共混羊毛蛋白納米纖維藥膜的緩釋功能及其對結腸癌細胞的體外抑制效果。
方法  將PLLA與羊毛蛋白共混交聯(lián),并加入抗腫瘤藥物5-FU,利用高壓靜電紡絲技術將共混溶液制作成具有緩釋效果的納米纖維薄膜。通過掃描電鏡(SEM)觀察其形貌。以高效液相色譜法(HPLC)測定5-FU/PLLA羊毛蛋白藥膜中5-FU的緩釋效果。采用噻唑藍(MTT)比色法,檢測藥膜對結腸癌細胞HCT116的體外殺傷效果。同時采用倒置相差顯微鏡、透射電子顯微鏡(TEM)觀測實驗組細胞的生長情況。
結果  由SEM可以看出5-FU能夠均勻分布在納米纖維藥膜中,HPLC顯示5-FU能夠緩慢釋放并基本符合零級動力學規(guī)律。采用不同處理因素后,通過顯微鏡觀察,藥膜浸泡時間越長的實驗組細胞出現(xiàn)腫脹、凋亡、壞死的情況越明顯。MTT檢測納米藥膜實驗組的細胞存活率為(47.5±2.8)%,而不含藥物的純膜組對細胞基本無影響,其存活率為(93.9±2.8)%,差異具有統(tǒng)計學意義(P<0.01)。
結論  5-FU/PLLA羊毛蛋白納米藥膜有明顯緩釋效果,具有較好的腫瘤細胞抑制作用和潛在的醫(yī)療應用價值。

引用本文: 談蘊璞,李剛,吳小劍,何小文,柯嘉,張晶,蘭平. 5-氟尿嘧啶納米藥膜的體外緩釋及其對結腸癌細胞抑制作用研究. 中國普外基礎與臨床雜志, 2012, 19(6): 610-615. doi: 復制

版權信息: ?四川大學華西醫(yī)院華西期刊社《中國普外基礎與臨床雜志》版權所有,未經(jīng)授權不得轉載、改編

1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010 [J]. CA Cancer J Clin, 2004, 60(5):277-300.
2. Zheng S, Cai SR . Colorectal cancer epidemiology and prevention study in China [J]. Chinese-German J Clin Oncol, 2003,2(2):72-75.
3. 吳在德, 吳肇漢. 外科學[ M]. 第6 版. 北京:人民衛(wèi)生出版社, 2005:510-515.
4. Pinedo HM, Peters GF. Fluorouracil:biochemistry and pharmacology [J]. J Clin Oncol, 1988, 6(10):1653-1664.
5. Matsuoka H, Ueo H, Sugimachi K, et al. Preliminary evidence that incorporation of 5-fluorouracil into RNA correlates with antitumor response [J]. Cancer Invest, 1992, 10(4):265-269.
6. Lokich JJ, Ahlgren JD, Gullo JJ, et al. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma:a Mid-Atlantic Oncology Program Study [J]. J Clin Oncol, 1989,7(4):425-432.
7. Rougier P, Paillot B, Laplanche A, et al. 5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration.Final results of a randomised trial in metastatic colorectal cancer [J]. Eur J Cancer, 1997, 33(11):1789-1793.
8. Gramont AD, Krulik M, Cady J, et al. High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer [J]. Eur J Cancer Clin Oncol, 1988, 24(9):1499-1503.
9. Frazier JL, Wang PP, Case D, et al. Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma [J]. J Neurooncol, 2003, 64(3):203-209.
10. 巴明臣, 崔書中, 駱福添, 等. 腹腔熱灌注化療治療進展期結直腸癌臨床療效及安全性的Meta 分析 [J]. 中國普外基礎與臨床雜志, 2010, 17(7):725-730.
11. Mumme AM, Laban S, Knecht R. New aspects of induction chemotherapy for head and neck cancer:POSTASCO 2011 [J].Eur Arch Otorhinolaryngol, 2012 Mar 25. [ Epub ahead of print].
12. Couch SM, Custer PL. Topical 5-fluorouracil for the treatment of periocular actinic keratosis and low-grade squamous malignancy [J]. Ophthal Plast Reconstr Surg, 2012 Mar 28. [Epubahead of print].
13. 陳萍, 施瑞華, 凌亭生. 磁性納米控釋紫杉醇對食管癌Eca109 細胞株生長的影響 [J]. 世界華人消化雜志, 2006,14(35):3348-3352.
14. 陳建民, 蔡寶英, 許力新, 等. 帶緩釋化療藥物食管支架對晚期食管癌的療效觀察[A]. 第九次全國消化系統(tǒng)疾病學術會議專題報告論文集[C], 2009:189-192.
15. Chiang CH, Tung SM, Lu DW, et al. In vitro and in vivo evaluation of an ocular delivery system of 5-fluorouracil microspheres [J]. J Ocul Pharmacol Ther, 2001, 17(6):545-553.
16. Maillard S, Ameller T, Gauduchon J, et al. Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and in vivo of anti-estrogens in human breast cancer and multiple myeloma [J]. J Steroid Biochem Mol Biol, 2005, 94(1-3):111-121.
17. Davies JM, Goldberg RM. Treatment of metastatic colorectal cancer [J]. Semin Oncol, 2011, 38(4):552-560.
18. Iwashyna TJ, Lamont EB. Effectiveness of adjuvant fluorouracil in clinical practice:a population-based cohort study of elderly patients with stage Ⅲ colon cancer [J]. J Clin Oncol, 2002,20(19):3992-3998.
19. Miyamoto T, Takahashi S, Ito H, et al. Tissue biocompatibility of cellulose and its derivatives [J]. J Biomed Mater Res, 1989,23(1):125-133.
20. Ho MH, Hou LT, Tu CY, et al. Promotion of cell affinity of porous PLLA scaffolds by immobilization of RGD peptides via plasma treatment [J]. Macromol Biosci, 2006, 6(1):90-98.
21. Xu XL, Chen XS, Xu XY, et al. BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells [J]. J Control Release, 2006, 114(3):307-316.
22. Gao H, Gu YQ, Ping QE. The implantable 5-fluorouracil-loaded poly (l-lactic acid) fibers prepared by wet-spinning from suspension [J]. J Control Release, 2007, 118(3):325-332.
23. Zhou J, Zhou Y, Yin B, et al. 5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro [J]. Oncol Rep, 2010, 23(1):121-128.
24. He BC, Gao JL, Zhang BQ, et al. Tetrandrine inhibits Wnt/β-catenin signaling and suppresses tumor growth of human colorectal cancer [J]. Mol Pharmacol, 2011, 79(2):211-219.
  1. 1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010 [J]. CA Cancer J Clin, 2004, 60(5):277-300.
  2. 2. Zheng S, Cai SR . Colorectal cancer epidemiology and prevention study in China [J]. Chinese-German J Clin Oncol, 2003,2(2):72-75.
  3. 3. 吳在德, 吳肇漢. 外科學[ M]. 第6 版. 北京:人民衛(wèi)生出版社, 2005:510-515.
  4. 4. Pinedo HM, Peters GF. Fluorouracil:biochemistry and pharmacology [J]. J Clin Oncol, 1988, 6(10):1653-1664.
  5. 5. Matsuoka H, Ueo H, Sugimachi K, et al. Preliminary evidence that incorporation of 5-fluorouracil into RNA correlates with antitumor response [J]. Cancer Invest, 1992, 10(4):265-269.
  6. 6. Lokich JJ, Ahlgren JD, Gullo JJ, et al. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma:a Mid-Atlantic Oncology Program Study [J]. J Clin Oncol, 1989,7(4):425-432.
  7. 7. Rougier P, Paillot B, Laplanche A, et al. 5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration.Final results of a randomised trial in metastatic colorectal cancer [J]. Eur J Cancer, 1997, 33(11):1789-1793.
  8. 8. Gramont AD, Krulik M, Cady J, et al. High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer [J]. Eur J Cancer Clin Oncol, 1988, 24(9):1499-1503.
  9. 9. Frazier JL, Wang PP, Case D, et al. Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma [J]. J Neurooncol, 2003, 64(3):203-209.
  10. 10. 巴明臣, 崔書中, 駱福添, 等. 腹腔熱灌注化療治療進展期結直腸癌臨床療效及安全性的Meta 分析 [J]. 中國普外基礎與臨床雜志, 2010, 17(7):725-730.
  11. 11. Mumme AM, Laban S, Knecht R. New aspects of induction chemotherapy for head and neck cancer:POSTASCO 2011 [J].Eur Arch Otorhinolaryngol, 2012 Mar 25. [ Epub ahead of print].
  12. 12. Couch SM, Custer PL. Topical 5-fluorouracil for the treatment of periocular actinic keratosis and low-grade squamous malignancy [J]. Ophthal Plast Reconstr Surg, 2012 Mar 28. [Epubahead of print].
  13. 13. 陳萍, 施瑞華, 凌亭生. 磁性納米控釋紫杉醇對食管癌Eca109 細胞株生長的影響 [J]. 世界華人消化雜志, 2006,14(35):3348-3352.
  14. 14. 陳建民, 蔡寶英, 許力新, 等. 帶緩釋化療藥物食管支架對晚期食管癌的療效觀察[A]. 第九次全國消化系統(tǒng)疾病學術會議專題報告論文集[C], 2009:189-192.
  15. 15. Chiang CH, Tung SM, Lu DW, et al. In vitro and in vivo evaluation of an ocular delivery system of 5-fluorouracil microspheres [J]. J Ocul Pharmacol Ther, 2001, 17(6):545-553.
  16. 16. Maillard S, Ameller T, Gauduchon J, et al. Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and in vivo of anti-estrogens in human breast cancer and multiple myeloma [J]. J Steroid Biochem Mol Biol, 2005, 94(1-3):111-121.
  17. 17. Davies JM, Goldberg RM. Treatment of metastatic colorectal cancer [J]. Semin Oncol, 2011, 38(4):552-560.
  18. 18. Iwashyna TJ, Lamont EB. Effectiveness of adjuvant fluorouracil in clinical practice:a population-based cohort study of elderly patients with stage Ⅲ colon cancer [J]. J Clin Oncol, 2002,20(19):3992-3998.
  19. 19. Miyamoto T, Takahashi S, Ito H, et al. Tissue biocompatibility of cellulose and its derivatives [J]. J Biomed Mater Res, 1989,23(1):125-133.
  20. 20. Ho MH, Hou LT, Tu CY, et al. Promotion of cell affinity of porous PLLA scaffolds by immobilization of RGD peptides via plasma treatment [J]. Macromol Biosci, 2006, 6(1):90-98.
  21. 21. Xu XL, Chen XS, Xu XY, et al. BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells [J]. J Control Release, 2006, 114(3):307-316.
  22. 22. Gao H, Gu YQ, Ping QE. The implantable 5-fluorouracil-loaded poly (l-lactic acid) fibers prepared by wet-spinning from suspension [J]. J Control Release, 2007, 118(3):325-332.
  23. 23. Zhou J, Zhou Y, Yin B, et al. 5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro [J]. Oncol Rep, 2010, 23(1):121-128.
  24. 24. He BC, Gao JL, Zhang BQ, et al. Tetrandrine inhibits Wnt/β-catenin signaling and suppresses tumor growth of human colorectal cancer [J]. Mol Pharmacol, 2011, 79(2):211-219.