5-氟脲嘧啶壳聚糖缓释微球对裸鼠腹腔种植胃癌细胞生长的抑制作用

谢小平; 易斌鸿; 端木尽忠; 李正荣; 陈文学; 揭志刚

doi:10.3969/j.issn.1000-8179.2011.03.003

摘要: 目的：观察5-氟脲嘧啶壳聚糖缓释微球对裸鼠腹腔内种植的胃癌细胞生长的抑制作用。方法：采用乳化交联法制备5-氟脲嘧啶壳聚糖缓释微球，测定微球的基本特性和体外缓释性能。32只裸鼠腹腔内种植了胃癌细胞后随机分为4组，分别植入5-氟脲嘧啶壳聚糖缓释微球、空白壳聚糖微球、5-氟脲嘧啶溶液和生理盐水。结果：所得5-氟脲嘧啶壳聚糖缓释微球的大小为（185.5±15.0）nm，药物包封率为（49.3±2.1）%；该微球在体外具有良好的药物缓释作用，用于腹腔化疗，并与其它3组比较，可明显改善腹腔内种植了胃癌细胞的裸鼠腹围和体重（P>0.05），减少腹腔癌结节数（P<0.05），增加腹水细胞的凋亡率（P<0.01），提高裸鼠的自然存活率（P<0.05），同时，药物的不良反应低（P<0.05）。结论：5-氟脲嘧啶壳聚糖缓释微球可有效地抑制裸鼠腹腔内种植的胃癌细胞生长，且用药安全。

Abstract: Inhibitory Effect of 5-Fluorouracil/Chitosan Drug-loaded Microspheres on the Growth of Peri-toneally Seeded Gastric Cancer Cells in Nude MiceXiaoping XIE1, Binhong YI1, Jinzhong DUANMU1, Zhengrong LI1,Wenxue CHEN2, Zhigang JIE1Correspondence to: Xiaoping XIE, E-mail: xply64@126.com1The Second Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China2Jiangsu Provincial Cancer Institute, Nanchang 330029, ChinaThis work was supported by the Research Fund from Department of Education of Jiangxi Province No. 2007(77)Abstract Objective: To observe the inhibitory effect of 5-fluorouracil-Chitosan microspheres on the growth of gastric cancercells peritoneally seeded in nude mice. Methods: The 5-fluorouracil-loaded chitosan release microspheres were prepared using theemulsion cross-link method. The basic characteristics and the release properties of the microspheres were determined in vitro. Thir-ty-two nude mice with peritoneally seeded gastric cancer cells were randomly divided into 4 groups: the mice in group A were intraperi-toneally implanted with 5-fluorouracil chitosan microspheres, group B were implanted with blank chitosan microspheres, group C wastreated with 5-fluorouracil, and group D received saline solution management. Results: The particle size and the drug encapsulation ef-ficiency of the 5-fluorouracil-loaded chitosan microspheres were 185.5 ± 15.0 nm and 49.3% ± 2.1%, respectively. The microspheresshowed a slower drug release profile in vitro. As for intraperitoneal chemotherapy, compared with the other 3 groups, 5-fluorouracil chi-tosan microspheres significantly decreased the abdominal circumference, increased the body weight of the treated nude mice ( P >0.05 ), and reduced the number of peritoneal cancerous foci ( P < 0.05 ). Treatment with 5-fluorouracil chitosan microspheres also in-creased the apoptosis rate of the gastric cancer cells in ascites ( P < 0.01 ) and improved the survival rate ( P < 0.05 ). Furthermore, thetoxicity of the treatment was rare ( P < 0.05 ). Conclusion: 5-fluorouracil chitosan microspheres for peritoneal chemotherapy can effec-tively inhibit the growth of intraperitoneal gastric cancer cells in nude mice ,with low rate of toxicity.Keywords 5-Fluorouracil; Chitosan microspheres; Intraperitoneal chemotherapy; Gastric cancer