Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic cancer growth in an orthotopic mouse model
Metrics: PDF 1269 views | HTML 1931 views | ?
In Kyong Shim1,*, Hye-Jin Yi1,*, Hee-Gyeong Yi2, Chan Mi Lee1, Yu Na Lee1, Yeong-Jin Choi3, Seong-Yun Jeong1, Eunsung Jun4,5, Robert M. Hoffman6,7, Dong-Woo Cho2 and Song Cheol Kim5
1 Asan Institute for Life Science, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
2 Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
3 Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
4 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea
5 Department of Surgery, University of Ulsan College of Medicine & Asan Medical Center, Seoul, South Korea
6 Department of Surgery, University of California, San Diego, CA, USA
7 AntiCancer Inc., San Diego, CA, USA
* These authors have contributed equally to this work
Song Cheol Kim, email:
Dong-Woo Cho, email:
Robert M. Hoffman, email:
Keywords: pancreatic cancer, orthotopic, nude mice, chemotherapy, patch
Received: March 10, 2017 Accepted: April 10, 2017 Published: April 22, 2017
To obtain improved efficacy against pancreatic cancer, we investigated the efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing polymeric patch was produced by 3D printing. After application of the patch, it released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was performed longitudinally. The drug patch delivered a 30.2 times higher level of 5-FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels were accumulated within one week by the patch. Four groups were compared for efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU-loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p. once a week (1.2 mg), three times (Group IV). The tumor growth rate was significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022 at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died of drug toxicity within two weeks after injection. Group II showed more effective suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day-21). Histological analysis showed extensive apoptosis in the TUNEL assay and by Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase-3 in Group II. No significant changes were found hematologically and histologically in the liver, kidney and spleen in Groups I, II, IV but were found in Group III.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.