Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor.
Two sublines, the hormone-sensitive LNCaP-FGC and the insensitive LNCaP-r (resistant) carcinoma cell lines, originating from the parental human prostatic carcinoma cell line LNCaP were tested for sensitivity to human tumor necrosis factor-alpha (TNF) using the MTT assay. Irrespective of the culture conditions, i.e., whether FGC cell growth was hormone stimulated or hormone deprived, a clear dose-related response was observed between the concentration of TNF (range: 5-5000 U/ml) in the culture medium and the percentage of growth inhibition. In medium containing androgen-depleted serum, in which FGC cells showed reduced proliferative activity, the percentage of inhibition by a concentration of 100 U/ml TNF was substantially higher than that found in hormone-stimulated cells (90% and 60%, respectively). In contrast to the FGC cells, the hormone-insensitive LNCaP-r cells were almost completely resistant to the action of TNF. Growth of the FGC cells was almost completely inhibited, whereas growth of the LNCaP-r cells was retarded with only 20% at dosages up to 5000 U/ml. This substantial difference in TNF responsiveness could not be ascribed to differences in TNF-binding capacity, as both the FGC and LNCaP-r cells were found to contain identical numbers of TNF-receptors (approximately 1000 sites/cell). A possible association between hormone responsiveness and TNF sensitivity is suggested for these LNCaP sublines.
Zhao
X
X
Department of Urology, Erasmus University, Rotterdam, The Netherlands.
van Steenbrugge
G J
GJ
Schröder
F H
FH
D000726:Androgen Antagonists / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004351:Drug Resistance; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D045165:Testosterone Congeners / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D000726:Androgen Antagonists; D003470:Culture Media; D045165:Testosterone Congeners; D014409:Tumor Necrosis Factor-alpha