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Differences in cell kinetic changes among renal cancer cell lines treated with interferon-alpha
Y Kasuya1, Y Hosaka, H Matsushima
1Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. kasuya@tmig.or.jp
Background:
Interferon (IFN)-alpha shows certain clinical effects on the treatment of renal cell carcinoma. The purpose of the present study was to investigate its direct effects and to compare the responses among different human renal cancer cell lines.
Methods:
Three cell lines, ACHN, RCC10RGB and OS-RC-2, were incubated with IFN-alpha and evaluated using MTT assay for cell proliferation and two-color flow cytometry for cell-cycle-specific cyclin expressions coupled with DNA ploidy analysis.
Results:
Interferon-alpha inhibited cell proliferation and caused cell accumulation at S and G2/M phases. However, IFN-alpha induced no significant change in cyclins D1, E, A or B1 expression. Interestingly, cell kinetic changes caused by IFN-alpha were different among cell lines. Cell proliferation was suppressed most in ACHN, then RCC10RGB and least in OS-RC-2. Comparing DNA histograms, ACHN showed distinct increase of G2/M cells associated with elevation of late S cells. RCC10RGB showed a predominant increase of whole S cells accompanied with a slight increase of G2/M. OS-RC-2 showed a modest increase of S cells with a little change of G2/M cells. Chronological observation revealed that S-phase increase and proliferative inhibition appeared on day 1 and day 3, respectively, in ACHN and RCC10RGB, and on day 5 in OS-RC-2.
Conclusions:
Interferon-alpha induced substantial cell kinetic interference directly in the tested human renal carcinoma cell lines. The degree of change was different according to the nature of the cell line. It may partly indicate the variety of the efficacy of IFN-alpha treatment against renal cancers.