Osteosarcoma is a common malignant bone tumor. Cisplatin (CDDP) achieves a high 
response rate in osteosarcoma. However, osteosarcoma usually exhibits cisplatin 
resistance. Many members of receptor tyrosine kinases (RTKs)(1) have been 
demonstrated to be overexpressed and constitutively activated in various tumors 
including osteosarcoma, resulting in malignant progression and insensitivity to 
chemotherapy. Hepatocyte growth factor receptor (HGFR/c-Met) also appears 
overexpressed and activated in osteosarcoma cells. Nevertheless, which role of 
c-Met activation in cisplatin efficacy against osteosarcoma cells remains still 
elusive. This study found that inhibition of c-Met activity by PHA-665752 or 
blockade of the interaction of autocrined HGF with c-Met with neutralizing 
anti-HGF antibody promoted cisplatin efficacy in osteosarcoma cells, while 
addition of recombinant human HGF (rh-HGF) counteracts cisplatin cytotoxicity. 
Specifically, we demonstrated that inhibition of c-Met activity led to 
suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity. 
Our study clearly suggests that inhibition of c-Met activity can effectively 
sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt 
signaling.