| Popis: |
This study investigates the involvement of apoptosis in the cytotoxic action of gemcitabine, a drug of widespread use for the treatment of pancreatic carcinoma. We show that 5/6 pancreatic carcinoma cell lines undergo DNA fragmentation and morphological changes typical for apoptosis following a 48-h exposure to gemcitabine (Gemzar® 0,1 –100 μg/ml). Apoptotic DNA fragmentation occurred in a dose-dependent manner and correlated with the expression level of the antiapoptotic Bel-xL protein. Treatment of Col0357 pancreatic carcinoma cells with specific antisense oligonueleotides against Bel-xL sensitized these cells to gemcitabine-induced apoptosis. Stable overexpression of Bel-xL in this cell line resulted in a strongly reduced sensitivity to gemcitabine-induced apoptosis. However, overexpression of the pro-apoptotic Bax protein that normally functions as a natural inhibitor of Bel-xL had no or only a marginal effect on the apoptotic response of these cells to gemcitabine. These data suggest that Bel-xL, but not Bax, may represent a useful prognostic factor for selecting patients who may benefit from gemcitabine treatment. |
