a Department of Internal Medicine , Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine , Seoul , South Korea.
b Department of Bionano Technology , Gachon University 65 , Bokjeongdong , Gyeong Gi-Do , South Korea.
Drug Deliv. 2018 Nov;25(1):872-879. doi: 10.1080/10717544.2018.1455760.
The aim of this study was to investigate the effectiveness of treating gastric cancer by injecting a pluronic F-127 sol-gel formulation of 5-fluorouracil (5-FU) into normal tissue surrounding the tumor using a hollow microneedle. The MTS tetrazolium assay was performed to assess the cytotoxicity of 5-FU after application to gastric cancer cells at different concentrations for 1, 5 and 10 h. Gastric cancer cells were inoculated subcutaneously into 30 male nude mice (CrjBALB/c-nu/nu mice, male); the inoculated mouse were divided into three groups. One group received no treatment, whereas the two other groups received free 5-FU gel (40 mg/kg) and 5-FU gel (40 mg/kg) for 4 days, respectively. Mean tumor volume, apoptotic index (TUNEL) and proliferative index (Ki 67) were evaluated in all groups. Cell viability was 77.3% when 1.22 g of free 5-FU was administered, whereas cell viability was 37.4% and 43.5% when 0.122 g of free 5-FU was administered per hour for 10 h and 0.244 g of free 5-FU was administered for 5 h (p < .01). The 5-FU sol-gel induced apoptosis and significantly inhibited cell proliferation compared to the free 5-FU (p < .01). In addition, xenografted tumor growth was significantly suppressed by administration of the 5-FU sol-gel formulation to inoculated mice (p < .01), and 71% (5/7) of xenografted tumors disappeared after 4 weeks. In conclusion, peri-tumor injection of a 5-FU sol-gel formulation into normal tissue surrounding the tumor mass using a hollow microneedle is an effective method for treating gastric cancer.
本研究旨在探讨通过中空微针将 5-氟尿嘧啶（5-FU）的 Pluronic F-127 溶胶-凝胶制剂注入肿瘤周围正常组织来治疗胃癌的效果。采用 MTS 四唑比色法评估不同浓度的 5-FU 作用于胃癌细胞 1、5 和 10 小时后的细胞毒性。将胃癌细胞皮下接种于 30 只雄性裸鼠（CrjBALB/c-nu/nu 小鼠，雄性）中；将接种的小鼠分为三组。一组未接受治疗，而另外两组分别接受游离 5-FU 凝胶（40mg/kg）和 5-FU 凝胶（40mg/kg）治疗，共 4 天。评估所有组的平均肿瘤体积、凋亡指数（TUNEL）和增殖指数（Ki 67）。当给予 1.22g 游离 5-FU 时，细胞活力为 77.3%，而当每小时给予 0.122g 游离 5-FU 持续 10 小时或给予 0.244g 游离 5-FU 持续 5 小时时，细胞活力分别为 37.4%和 43.5%（p<.01）。与游离 5-FU 相比，5-FU 溶胶凝胶诱导凋亡并显著抑制细胞增殖（p<.01）。此外，通过向接种小鼠施用 5-FU 溶胶凝胶制剂，异种移植瘤的生长明显受到抑制（p<.01），并且在 4 周后 71%（5/7）的异种移植瘤消失。总之，使用中空微针对肿瘤周围正常组织注射 5-FU 溶胶凝胶制剂是治疗胃癌的有效方法。
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