Sensitization of Osteosarcoma Cell Line SaOS-2 to Chemotherapy by Downregulating Survivin

Zou, Jun; Gan, Minfeng; Mao, Nana; Zhu, Xuesong; Shi, Qin; Yang, Huilin

doi:10.1016/j.arcmed.2010.04.006

« Previous Next »Archives of Medical Research
Volume 41, Issue 3 , Pages 162-169, April 2010

Sensitization of Osteosarcoma Cell Line SaOS-2 to Chemotherapy by Downregulating Survivin

Jun Zou
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- These authors contributed equally to this work.
Minfeng Gan
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- These authors contributed equally to this work.
Nana Mao
- Department of Pharmacy, Suzhou School of Medial Science and Technology, Suzhou, Jiangsu, China
Xuesong Zhu
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Qin Shi
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Huilin Yang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Address reprint requests to: Huilin Yang, MD, Chairman & Professor, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi St., Suzhou, Jiangsu 215006, China; Phone: +86-512-67780101; FAX: +86-512-67780999

Received 24 September 2009; accepted 7 February 2010.

(ARCMED-D-09-00448)

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.

Key Words: Osteosarcoma, Survivin, Chemotherapy, Sensitization