Received for publication January 3, 2008.
Revised January 31, 2008.
Accepted for publication January 31, 2008.

Statin-induced inhibition of HMG-CoA reductase sensitizes human osteosarcoma cells to anticancer drugs

Abstract

Osteosarcoma is the most common primary bone tumor in children and young adults. Resistance to chemotherapeutic drugs is a major problem that is responsible for the failure of treatment. This points to the need for increasing the responsiveness to cytotoxic drugs. We previously showed that lipophilic statins induce apoptosis in human osteosarcoma cells. Here, we investigated the effects of atorvastatin in combination with chemotherapeutic drugs on human osteosarcoma cell apoptosis, invasion and migration. We report here that atorvastatin enhances the reduced cell viability induced by the anti-cancer drugs doxorubicin and cisplatin in human osteosarcoma cells. Specifically, we found that atorvastatin enhances the induction of osteosarcoma cell apoptosis by anticancer drugs. Additionally, we show that atorvastatin enhances the inhibitory effect of anticancer drugs on osteosarcoma cell migration. Moreover, atorvastatin and chemotherapeutic drugs had additive inhibitory effects on osteosarcoma cell invasion. Consistently, atorvastatin further augmented the reduction of MMP2 activity induced by doxorubicin or cisplatin in osteosarcoma cells. The results show for the first time that atorvastatin sensitizes osteosarcoma cells to anticancer drugs, resulting in reduced cell viability, migration and invasion, which suggests a strategy to improve the response to chemotherapy and reduce tumorigenesis in human osteosarcoma.

Key words: MMP2, Osteosarcoma, anticancer drugs, invasion, migration, statin