5-FU Loaded Nanofibers Membrane for Controlled Release Effect Against Colon Cancer Cell in Vitro_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

TAN Yunpu ¹ , LI Gang ² , WU Xiaojian ¹ , HE Xiaowen ¹ , KE Jia ¹ , ZHANG Jing ² , LAN Ping. ¹

1. Department of Colorectal Surgery,The Sixth Affiliated Hospital, SUN Yat-sen University, Guangzhou 510655, Guangdong Province, China;;
2. Institute of Textiles &;
Clothing, The Hong Kong Polytechnic University, Hong Kong, China;

Corresponding author：

Keywords：

Nanofibers membrane; Anti-cancer; 5-FU; Poly-L-lactic acid; HCT116 cell

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Objective 　To investigate the controlled release effect and the anti-cancer cell ability of a 5-FU loaded poly-L-lactic acid （PLLA） nanofibers membrane blending with keratin.
Methods 　Making PLLA and keratin mix together and crosslinking to generate blending solution. Then the anti-cancer drug 5-FU was added into the solution to fabricate nanofibers membrane by high voltage electrospinning method. The micro morphology was observed by scanning electron microscope （SEM）. The controlled release effect of 5-FU from the nanofibers membrane was measured by high performance liquid chromatography （HPLC）. The cytotoxicity of 5-FU/PLLA keratin nanofibers membrane was evaluated by using 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay on HCT116 cell lines. At the meantime, cell growth morphology of HCT116 in experiment group were observed by microscope and transmission electron microscope.
Results 　5-FU could be dispersed homogeneous in the PLLA/keratin nanofibers membrane through SEM. HPLC suggested that 5-FU could be diffused out from the fibers slowly and uniformly, which corresponded the zero order kinetics basically. After different treatment, the longer time the 5-FU/PLLA keratin nanofibers （experiment group） immerse in the medium, the much more swelling, apoptosis, and necrocytosis of the cells were observed. The cell viability for experiment group was （47.5±2.8）% by MTT, while the PLLA keratin nanofibers without 5-FU had no significant impact on cell viability （93.9±2.8）%, which was statistic significance （P＜0.01）.
Conclusion 　5-FU/PLLA keratin nanofibers membrane owns good controlled release effect and satisfies cell inhibitory effect against HCT116 cells in vitro，which suggested that it has a promising prospect for clinical therapy.

Citation： TAN Yunpu,LI Gang,WU Xiaojian,HE Xiaowen,KE Jia,ZHANG Jing,LAN Ping.. 5-FU Loaded Nanofibers Membrane for Controlled Release Effect Against Colon Cancer Cell in Vitro. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(6): 610-615. doi: Copy

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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. 吴在德，吴肇汉. 外科学[ M]. 第6 版. 北京：人民卫生出版社， 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，崔书中，骆福添，等. 腹腔热灌注化疗治疗进展期结直肠癌临床疗效及安全性的Meta 分析 [J]. 中国普外基础与临床杂志， 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. 陈萍，施瑞华，凌亭生. 磁性纳米控释紫杉醇对食管癌Eca109 细胞株生长的影响 [J]. 世界华人消化杂志， 2006，14(35)：3348-3352.
14. 陈建民，蔡宝英，许力新，等. 带缓释化疗药物食管支架对晚期食管癌的疗效观察[A]. 第九次全国消化系统疾病学术会议专题报告论文集[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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

5-FU Loaded Nanofibers Membrane for Controlled Release Effect Against Colon Cancer Cell in Vitro

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