Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells

Y. Miyamoto, R. Hosotani, R. Doi, M. Wada, J. Ida, S. Tsuji, M. Kawaguchi, S. Nakajima, H. Kobayashi, T. Masui, M. Imamura

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

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 α subunit) in all pancreatic cancer cell lines except in AsPC-1. When immunoprecipitation was performed, the bands indicating phosphorylated gp130 (IL-6R β) 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 CFPAC-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. II-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.

Original languageEnglish
Pages (from-to)2449-2456
Number of pages8
JournalAnticancer research
Volume21
Issue number4 A
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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