Antitumor activity of cationic liposome-mediated Bax gene transfer in osteosarcoma cells: induction of apoptosis and caspase-independent cell death

• Published in: International journal of oncology Vol. 27; no. 2; p. 433
• Main Authors: Okumura, Kenya, Nakase, Minoru, Nakamura, Shinnosuke, Inui, Madoka, Hiramoto, Kenichi, Tagawa, Toshiro
• Format: Journal Article
• Language: English
• Published: Greece 01.08.2005
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; Blotting, Western; Caspase 3; Caspase 9; Caspase Inhibitors; Caspases - metabolism; Cations - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Humans; In Situ Nick-End Labeling; Liposomes - chemistry; Osteosarcoma - enzymology; Osteosarcoma - genetics; Osteosarcoma - pathology; Transfection - methods
• ISSN: 1019-6439
• DOI: 10.3892/ijo.27.2.433

The purpose of this study was to evaluate the anti-tumor effects of osteosarcoma (HOSM-1) cells via transfer of the Bax gene using a cationic liposome. We evaluated the levels of Bax, Bcl-xL, Bcl-2 and cytochrome c expression by Western blot analysis, and caspase-9 and -3 activities were determined in a colorimetric assay. Apoptosis was detected using a TUNEL assay, and cell growth inhibition was determined in an MTT assay. Following Bax gene transfer, release of cytochrome c to the cytosol was detected, the activities of caspase-9 and -3 increased, and TUNEL-positive cells (37.5%) were detected. Cell survival rate was 50.8% under these conditions. Induction of apoptosis was inhibited by a caspase inhibitor (zVAD-fmk), but only a slight increase in cell survival rate occurred. Hence, since not only apoptosis but also caspase-independent cell death is induced in HOSM-1 cells, we anticipate that Bax gene therapy with cationic liposomes will be useful for osteosarcoma.