Sensitization of osteosarcoma cell line SaOS-2 to chemotherapy by downregulating survivin.

BACKGROUND AND AIMS

Osteosarcoma is the most frequent malignant bone tumor with a peak incidence in the second and third decades of life. Survivin, a member of the IAP family of proteins, is overexpressed in osteosarcomas and plays an important role in protecting cells from apoptosis. Here we investigated the anti-cancer effects of downregulating survivin by shRNA vector pSUPER-sh in combination with chemotherapeutic drugs on human osteosarcoma cells.

METHODS

Expression of survivin was detected by Western blot. The effects of pSUPER-sh and chemotherapeutic drugs on osteosarcoma cell lines Saos-2 and U2OS by cell viability assay and its underlying mechanisms were analyzed by flow cytometry and caspase-3 activity assay.

RESULTS

Downregulated survivin could significantly induce apoptosis of osteosarcoma cell lines Saos-2 and U2OS. The effect probably resulted from downregulation of survivin induced by pSUPER-sh. Importantly, we found that the downregulation of survivin by pSUPER-sh could enhance the anticancer effects of chemotherapies such as etoposide, cisplatin and doxorubicin through decreasing mitochondrial membrane potentials and increasing caspase-3 activity.

CONCLUSIONS

Downregulated survivin by pSUPER-sh could markedly induce apoptosis of osteosarcoma cells lines and pSUPER-sh may be a promising adjuvant in osteosarcoma chemotherapy.