Effects of gemcitabine on cell proliferation and apoptosis in non-small-cell lung cancer (NSCLC) cell lines.
We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 microM gemcitabine for 24, 48 and 72 h, respectively. Gemcitabine exerted a stronger and earlier antiproliferative and proapoptotic effect on H292 cells than on CorL23 or Colo699 cells. Fas receptor expression was increased in all three cell lines and was higher in Colo699 than in CorL23 cells. The incubation of NSCLC with anti-Fas agonistic monoclonal antibody (CH11) induced cell apoptosis in H292 cells, demonstrating that the Fas receptor was functionally active. Finally, gemcitabine and CH-11 exerted a synergistic effect on cell apoptosis in H292 cells. This study demonstrates that gemcitabine induces apoptosis in NSCLC and that this effect might be exerted by modulating functionally active Fas expression, and these effects of gemcitabine were stronger in H292 cells than in either CorL23 or Colo699 cells.
Pace
E
E
Italian National Research Council, Institute of Respiratory Pathophysiology, Via Trabucco 180, 90146 Palermo, Italy. pace@ifr.pa.cnr.it
Melis
M
M
Siena
L
L
Bucchieri
F
F
Vignola
A M
AM
Profita
M
M
Gjomarkaj
M
M
Bonsignore
G
G
D000951:Antigens, Neoplasm / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects*; D053938:DNA Fragmentation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D019014:fas Receptor / Q000032:analysis; D000093542:Gemcitabine
D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D019014:fas Receptor; D003841:Deoxycytidine; D000093542:Gemcitabine