Abstract | BACKGROUND: METHODS: RESULTS: The drug-release study showed that the increased drug content on the PCL film induced a faster drug-release rate. The growth of cancer cells on the sorafenib-loaded PCL film surfaces decreased in a dose-dependent manner. MMP-2 expression of HuCC-T1 cells gradually decreased according to sorafenib concentration. Furthermore, cancer cell invasion and tube formation of human umbilical vein endothelial cells significantly decreased at sorafenib concentrations higher than 10 mM. In the mouse tumor xenograft model with HuCC-T1 cells, sorafenib-eluting PCL films significantly inhibited the growth of tumor mass and induced apoptosis of tumor cells. Various molecular signals, such as B-cell lymphoma (Bcl)-2, Bcl-2-associated death promoter, Bcl-x, caspase-3, cleaved caspase-3, Fas, signal transducer and activator of transcription 5, extracellular signal-regulated kinases, MMP-9 and pan- janus kinase/ stress-activated protein kinase 1, indicated that apoptosis, inhibition of growth and invasion was cleared on sorafenib-eluting PCL films. CONCLUSION: These sorafenib-loaded PCL films are effective in inhibiting angiogenesis, proliferation and invasion of cancer cells. We suggest that sorafenib-loaded PCL film is a promising candidate for the local treatment of cholangiocarcinoma.
|
Authors | Do Hyung Kim, Young-Il Jeong, Chung-Wook Chung, Cy Hyun Kim, Tae Won Kwak, Hye Myeong Lee, Dae Hwan Kang |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 8
Pg. 1697-711
( 2013)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 23658488
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents
- Phenylurea Compounds
- Polyesters
- polycaprolactone
- Niacinamide
- Sorafenib
- Matrix Metalloproteinase 2
|
Topics |
- Animals
- Antineoplastic Agents
(chemistry, pharmacokinetics, pharmacology)
- Bile Duct Neoplasms
- Bile Ducts, Intrahepatic
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Cholangiocarcinoma
- Drug Evaluation, Preclinical
- Drug-Eluting Stents
- Human Umbilical Vein Endothelial Cells
- Humans
- Male
- Matrix Metalloproteinase 2
(metabolism)
- Mice
- Mice, Nude
- Niacinamide
(analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
- Phenylurea Compounds
(chemistry, pharmacokinetics, pharmacology)
- Polyesters
- Sorafenib
- Xenograft Model Antitumor Assays
|