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LIM kinase 1 is required for insulin-dependent cell growth of osteosarcoma cell lines
- Source :
- Molecular Medicine Reports. 9:103-108
- Publication Year :
- 2013
- Publisher :
- Spandidos Publications, 2013.
-
Abstract
- Osteosarcoma is a type of malignant bone tumor with high metastasis and poor prognosis. Previous studies have demonstrated the involvement of LIM kinase 1 (LIMK1) in the proliferation of osteosarcoma cells. LIMK1 is overexpressed in human osteosarcoma tissues and cell lines. To further study LIMK1-associated mechanisms, we used shRNA targeted to the LIMK1 gene to block its expression in the osteosarcoma cell lines MG63 and U2OS. Insulin promoted the proliferation of MG63 cells in a time- and dose-dependent manner, however, this insulin induced proliferation was significantly inhibited by transfection of shRNA targeted to the LIMK1 gene, as well as by the PI3K inhibitor LY294002, but not by the mitogen‑activated protein kinase (MAPK) inhibitor PD98059. The level of cofilin phosphorylation was increased significantly following stimulation of insulin for 24 h, indicating the activation of LIMK1. MG63 cell proliferation was also significantly inhibited by 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in a time-dependent manner. Furthermore, 1,25(OH)2D3 negated the inhibitory effect of LIMK1 shRNA, indicating that LIMK1 is important in the inhibitory pathway of 1,25(OH)2D3. The present study confirms that LIMK1 is important in regulating osteosarcoma cell proliferation via the insulin/PI3K/LIMK1 signaling pathway, thus the development of gene therapy for osteosarcoma targeting LIMK1 is warranted.
- Subjects :
- Cancer Research
Morpholines
LIMK1
Biology
Biochemistry
Lim kinase
Phosphatidylinositol 3-Kinases
Cell Line, Tumor
Genetics
medicine
Humans
Insulin
Phosphorylation
RNA, Small Interfering
Protein kinase A
Protein Kinase Inhibitors
Molecular Biology
PI3K/AKT/mTOR pathway
Cell Proliferation
Cholecalciferol
Phosphoinositide-3 Kinase Inhibitors
Flavonoids
Osteosarcoma
Cell growth
Lim Kinases
Cell cycle
medicine.disease
Cell biology
Actin Depolymerizing Factors
Oncology
Chromones
Cancer research
Molecular Medicine
RNA Interference
Mitogen-Activated Protein Kinases
A431 cells
Signal Transduction
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....954b4cd7d64c73172eae078b4e6c91e1