Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2.
To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl2. SBC-3/Bcl2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3, with relative resistance values of 3.4, 7.6 and 5.7, respectively. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and taxol between SBC-3 and SBC-3/Bcl2. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC, in a concentration-dependent manner. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl2. Treatment with CDDP resulted in the same degree of DNA fragmentation in SBC-3 and SBC-3/Bcl2. These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis.
Ohmori
T
T
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Podack
E R
ER
Nishio
K
K
Takahashi
M
M
Miyahara
Y
Y
Takeda
Y
Y
Kubota
N
N
Funayama
Y
Y
Ogasawara
H
H
Ohira
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001483:Base Sequence; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D016685:Mitomycin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016685:Mitomycin; D000077146:Irinotecan; D004317:Doxorubicin; D002166:Camptothecin