Back to Search
Start Over
FTY720, a synthetic compound from Isaria sinclairii, inhibits proliferation and induces apoptosis in pancreatic cancer cells.
- Source :
-
Cancer letters [Cancer Lett] 2007 Sep 08; Vol. 254 (2), pp. 288-97. Date of Electronic Publication: 2007 Apr 25. - Publication Year :
- 2007
-
Abstract
- FTY720, a synthetic compound produced by modification of a metabolite from Isaria sinclairii, is known as a unique immunosuppressive agent that exerts its activity by inducing apoptosis of lymphocytes [S. Suzuki, FTY720: Mechanisms of action and its effect on organ transplantation, Transplant. Proc. 31 (1999) 2779-2782]. Additionally, it has been found that FTY720 has inhibitory effects on various cancer growth and metastasis [J.D. Wang, S. Takahara, N. Nonomura, Early induction of apoptosis in androgen-independent prostate cancer cell line by FTY720 requires caspase-3 activation, Prostate 40 (1999) 50-55]. To investigate its effect on the growth and metastasis of pancreatic cancer, FTY720 was used to treat three pancreatic cancer cell lines (BxPC-3, AsPC-1, and PANC-1). The MTT assay and flow cytometry were used to evaluate the cell death after FTY720 treatment; the wound closure assay, three-dimensional (3D) Matrigel assay, and invasive assay were used to evaluate the migration, colony formation and invasion abilities after FTY720 treatment, respectively. Protein expression in BxPC-3, AsPC-1, and PANC-1 cells after FTY720 treatment was detected by Western blotting. The MTT assay indicated that the growth of pancreatic cancer cells could be inhibited by FTY720 at various concentrations between 0 and 17 microM in a dose-dependent manner, which was also confirmed by flow cytometry. The wound closure assay, 3D Matrigel assay and cell invasion assay all showed that FTY720 significantly suppressed migration, colony formation and invasion ability of cancer cells at concentrations from 5 to 17 microM. After FTY720 treatment, the phospho-Akt, Bcl-2, pro-caspase-3 expression were down-regulated while the caspase-9 protein expression was increased. In conclusion, FTY720 can inhibit the growth, migration and invasion of pancreatic cancer cells. Our study provides a preclinical support for chemotherapeutic approach with FTY720 for the treatment of pancreatic cancer.
- Subjects :
- Adenocarcinoma pathology
Ascomycota
Cell Line, Tumor
Fingolimod Hydrochloride
Humans
Immunosuppressive Agents pharmacology
Propylene Glycols isolation & purification
Sphingosine isolation & purification
Sphingosine pharmacology
Wound Healing drug effects
Apoptosis drug effects
Cell Division drug effects
Pancreatic Neoplasms pathology
Propylene Glycols pharmacology
Sphingosine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0304-3835
- Volume :
- 254
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 17462818
- Full Text :
- https://doi.org/10.1016/j.canlet.2007.03.013