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

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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 - 24-11-2001

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Miyamoto, Y., Hosotani, R., Doi, R., Wada, M., Ida, J., Tsuji, S., Kawaguchi, M., Nakajima, S., Kobayashi, H., Masui, T., & Imamura, M. (2001). Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells. Anticancer research, 21(4 A), 2449-2456.