Role of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-X) on cellular susceptibility to radiation in pancreatic cancer cells.
The aim of this study was to examine Bax, Bcl-2 and Bcl-XL proteins in human pancreatic cancer cell lines and to clarify the mechanism of radiation resistance. PANC-1 and AsPC-1 pancreatic cell lines were used, both having mutated p53. Radioresistant PANC-1/Rad cells and AsPC-1/Rad cells were obtained by repeated 5 Gy irradiation of PANC-1 cells and AsPC-1 cells, respectively. Radiation was found to inhibit the growth of PANC-1 cells and AsPC-1 cells. After exposure to radiation, detached cells were subjected to FITC-TUNEL staining to calcualte the ratio of apoptosis. TUNEL positive ratios increased dose-dependently in both cell lines. Western blotting showed that the basal level of the Bax/Bcl-2 ratio reflected the radiosensitivity of these cell lines, and Bax expression was obviously upregulated after irradiation in the presence of mutated p53, but Bcl-2 expression remained almost constant. Both PANC-1/Rad and AsPC-1/Rad cells had greater Bcl-XL expression than the parental cells, and the basal level of the Bax/Bcl-2 ratio was no longer predictive of radiosensitivity. Upregulated expression of Bax protein after irradiation was not related to induction of apoptosis in these cells, suggesting that overexpression of Bcl-XL and functional reconstruction of Bcl-2 family proteins are important factors in acquired radioresistance.
Lee
J U
JU
Department of Surgery and Surgical Basic Science, Kyoto University, Japan.
Hosotani
R
R
Wada
M
M
Doi
R
R
Kosiba
T
T
Fujimoto
K
K
Miyamoto
Y
Y
Tsuji
S
S
Nakajima
S
S
Nishimura
Y
Y
Imamura
M
M
D015153:Blotting, Western; D006801:Humans; D009154:Mutation / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D011836:Radiation Tolerance; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2