Inhibiting proliferation and enhancing chemosensitivity to taxanes in osteosarcoma cells by RNA interference-mediated downregulation of stathmin expression.
Stathmin (Oncoprotein18), a signal transduction regulatory factor, plays an important role in cell division and malignant tumor development. Stathmin is a ubiquitous intracellular phosphoprotein that is overexpressed in a variety of human malignancies, including osteosarcoma. To investigate the potential use of stathmin as a therapeutic target for human osteosarcomas, we employed RNA interference [small interfering RNA (siRNA)] to reduce stathmin expression in human osteosarcoma cell lines and analyzed their phenotypic changes. Results showed that the downregulation of stathmin expression in human osteosarcoma cells significantly inhibited cell proliferation in vitro and tumorigenicity in vivo. The specific downregulation induced cell arrest in the G(2)/M phase of cell cycle and eventually apoptotic cell death. Taxanes are a group of effective chemotherapeutic agents whose activity is mediated through stabilization of the microtubules of the mitotic spindle. In the present study, we also observed a synergistic enhancement of the cytotoxicity effect by combination use of taxanes and RNA interference-mediated stathmin downregulation. All these experimental data indicate that stathmin downregulation can lead to potent antitumor activity and chemosensitizing activity to taxanes in human osteosarcomas.
Wang
Rui
R
Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Dong
Ke
K
Lin
Fang
F
Wang
Xi
X
Gao
Ping
P
Wei
San-Hua
SH
Cheng
Shi-Yin
SY
Zhang
Hui-Zhong
HZ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017931:DNA Primers; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D050777:Stathmin / Q000235:genetics*; D043823:Taxoids / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D050777:Stathmin; D043823:Taxoids