Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells.
We have examined the relationship between the expression and activation of the IL-6 receptor and the possible involvement of IL-6 in the resistance of radiation-induced apoptosis in pancreatic cancer cells. Levels of IL-6 in the incubation media measured with ELISA were 1900 pg/ml in CFPAC-1, 54 pg/ml in HPAC and less than 0.2 pg/ml in MIAPaCa-2 and AsPC-1. Western blot demonstrated gp80 protein (IL-6 receptor a subunit) in all pancreatic cancer cell lines except in AsPC-1. When immunoprecipitation was performed, the bands indicating phosphorylated gp130 (IL-6Rbeta) were observed in CFPAC-1 and HPAC, however, no band was found in MIAPaCa-2 or in AsPC-1 cells. RT-PCR and Western blot demonstrated that mRNA and protein expression for Bcl-2 and Bcl-XL was substantially increased by the IL-6 treatment in CEPAC-1 cells, but not in AsPC-1 cells. Neither exogenous IL-6 nor neutralizing anti-IL-6 mAb affected the proliferation of CFPAC-1 and AsPC-1 cells. However, the IL-6 treatment significantly attenuated the susceptibility to radiation in CFPAC-1 cells but not in AsPC-1 cells, and the neutralizing anti-IL-6 mAb significantly increased the radiosensitivity of CFPAC-1 cells. The results indicated that IL-6 might be produced in a paracrine and/or autocrine fashion in pancreatic cancer cells. In-6 inhibits radiation-induced apoptosis and enhances the survival of the cells through a functional receptor system, which is associated with the up-regulation of anti-apoptotic Bcl-2 family proteins, especially Bcl-XL.
Miyamoto
Y
Y
Department of Surgery and Surgical Basic Science, Kyoto University, Japan. yshr@kuhp.kyoto-u.ac.jp
Hosotani
R
R
Doi
R
R
Wada
M
M
Ida
J
J
Tsuji
S
S
Kawaguchi
M
M
Nakajima
S
S
Kobayashi
H
H
Masui
T
T
Imamura
M
M
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014443:Tyrosine