Sensitization of osteosarcoma cell line SaOS-2 to chemotherapy by downregulating survivin.
OBJECTIVE
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.
Zou
Jun
J
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Gan
Minfeng
M
Mao
Nana
N
Zhu
Xuesong
X
Shi
Qin
Q
Yang
Huilin
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D005047:Etoposide; D004317:Doxorubicin; C505407:CASP3 protein, human; D053148:Caspase 3; D002945:Cisplatin