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:
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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.