Orthopedics Medical News about osteosarcoma growth;notch pathway;cell cycle regulation

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Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation
British Journal of Cancer, 05/29/09

Tanaka M et al. - In a study to determine how the Notch pathway is involved in the pathogenesis of osteosarcoma, it was concluded that inhibition of Notch pathway suppresses osteosarcoma growth by regulation of cell cycle regulator expression and that the inactivation of the Notch pathway may be a useful approach to the treatment of patients with osteosarcoma.

Methods

Expression of the Notch pathway molecules was investigated in osteosarcoma biopsy specimens and the effect of Notch pathway inhibition was examined.

Results

Real-time PCR revealed overexpression of Notch2, Jagged1, HEY1, and HEY2.
Notch1 and DLL1 were downregulated in biopsy specimens.
Notch pathway inhibition using γ-secretase inhibitor and CBF1 siRNA slowed the growth of osteosarcomas in vitro.
γ-secretase inhibitor-treated xenograft models exhibited significantly slower osteosarcoma growth.
Cell cycle analysis revealed that γ-secretase inhibitor promoted G1 arrest.
Real-time PCR and western blot revealed that γ-secretase inhibitor reduced the expression of accelerators of the cell cycle, including cyclin D1, cyclin E1, E2, and SKP2.
p21cip1 protein, a cell cycle suppressor, was upregulated by γ-secretase inhibitor treatment.

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