Mechanism of bortezomib in inducing apoptosis and improving chemosensitivity of Ishikawa cells / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of bortezomib on the apoptosis and drug sensitivity of endometrial cancer cell line Ishikawa cells.</p><p><b>METHODS</b>The IC50 of bortizomib, ADR, DDP and PTX in Ishikawa cells was determined using MTT method. After treatment with IC50 bortezomib for 6 and 12 h, the expressions of caspases-3, caspases-9 and bcl-2 genes were detected by RT-PCR, and the cell apoptotic rate and ROS level Ishikawa cells were evaluated by flow cytometry after treatment with half of the IC50 of the drugs for 24 h.</p><p><b>RESULTS</b>The IC50 of bortizomib, ADR, DDP, and PTX was 71.6 nmol/L, 0.572 micromol/L, 67.4 micromol/L and 719.5 nmol/L, respectively. Bortizomib significantly increased the mRNA expressions of caspases-3 and caspases-9 but decreased the expression of bcl-2. Compared with the treatment with agents alone, combined treatment of the cells significantly improved the cytotoxicity of the chemotherapeutic agents (P<0.05) and increased the ROS level and the apoptosis of the cells.</p><p><b>CONCLUSION</b>Bortizomib can inhibit the protein kinase to induce the apoptosis and enhance the chemosensitivity of Ishikawa cells.</p>