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KMID : 1001020030010010112
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Journal of Urologic Oncology
2003 Volume.1 No. 1 p.112 ~ p.117
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The Effect of Growth Factors and Cytokines on Cell Growth of Androgen Sensitive and Insensitive Human Prostate Cancer Cells in vitro
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Youn Nae-Young
Lee Hyung-Lae
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Abstract
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Purpose: It is established that growth factors (GFs) and cytokines exert a wide spectrum of activities on many different human prostate cancer cell lines. Early staged prostate cancer responds to androgen suppression therapies. However, the resulting disseminated disease is characterized by androgen insensitivity and autonomous growth. In this study, the growth response of androgen sensitive cell lines was compared to the response of androgen insensitive cell lines in an effort to determine the role GFs and cytokines play in the development of tumor progression in prostate cancer patients.
Materials and Methods: Seven human prostate carcinoma cell lines were studied that were androgen sensitive cells (LNCap, DuCaP, VCaP, MDA-2a, MDA-2b) and androgen insensitive cells (PC-3, DU145). Cells were grown in 96-well plates for 24 hours. After this period, media containing the respective GFs and cytokines (PDGF, IGF-I, TGF-β, EGF, bFGF, TNF-α, IL-1, and IL-6) were added for 48 hours. Relative cell growth rates were then determined by mitochondrial dehydrogenase activity using WST-1 (Roche, Mannheim, Germany).
Results: Androgen insensitive human prostate cancer cell lines did not respond to IGF-1, TGF-β, bFGF, TNF-α, IL-1, and IL-6. EGF preferentially stimulated brain-derived DU145 cell growth. PC-3 cell growth was significantly stimulated by low dose PDGF (0.1-1ng/ml). PDGF and bFGF had variable effects on androgen sensitive prostate cancer cell lines. IL-1 stimulated the growth of MDA-2a and MDA-2b cell lines in a dose dependent manner. TNF-α preferentially inhibited proliferation of the VCaP cells. Lymph node-derived LNCaP cell growth was stimulated by IGF-1, TGF-β, TNF-α, and IL-6. However, DuCaP cells derived from brain metastasis, failed to respond to any of the selected GFs and cytokines.
Conclusions: These findings demonstrate that androgen sensitive human prostate cancer cell lines seem to be more sensitive to exogenous GFs and cytokines than androgen insensitive cell lines. In conclusion, this study suggests that the sensitivity of prostate cancer cells to various GFs and cytokines is heterogenous.
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KEYWORD
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Prostate cancer, Growth factors, Cytokines, Androgen receptor
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