LIM kinase 1 is required for insulin‑dependent cell growth of osteosarcoma cell lines.

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.

• Authors: Hai-Shan Zhang, Jian-Wu Zhao, Hong Wang, Han-Yang Zhang, Qiu-Ye Ji, Ling-Jie Meng, Feng-Juan Xing, Shu-Ting Yang, Yan Wang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 9 Issue 1 Pg. 103-8 (Jan 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 24247826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actin Depolymerizing Factors
• Chromones
• Flavonoids
• Insulin
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• RNA, Small Interfering
• Cholecalciferol
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• LIMK1 protein, human
• Lim Kinases
• Mitogen-Activated Protein Kinases
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Actin Depolymerizing Factors (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cholecalciferol (pharmacology)
• Chromones (pharmacology)
• Flavonoids (pharmacology)
• Humans
• Insulin (pharmacology)
• Lim Kinases (antagonists & inhibitors, genetics, metabolism)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Morpholines (pharmacology)
• Osteosarcoma (metabolism, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Signal Transduction (drug effects)