[Mechanism of bortezomib in inducing apoptosis and improving chemosensitivity of Ishikawa cells].
OBJECTIVE
To investigate the effect of bortezomib on the apoptosis and drug sensitivity of endometrial cancer cell line Ishikawa cells.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Bortizomib can inhibit the protein kinase to induce the apoptosis and enhance the chemosensitivity of Ishikawa cells.
Shen
Yuan
Y
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China. missyy@126.com
Hu
Hai-yan
HY
Lu
Lin
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004357:Drug Synergism; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D011480:Protease Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D001897:Boronic Acids; D011480:Protease Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D017382:Reactive Oxygen Species; D000069286:Bortezomib; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9