Περίληψη:
Objectives. Hormone-independent and cytotoxic drug-resistant tumor
growth in osteoblastic metastases defines poor survival in patients with
advanced prostate cancer. Therefore, we analyzed the ability of human
osteoblast-like cells (MG-63 cells) and MC-63 conditioned media (MG-63
CM) to protect PC-3 human prostate cancer cells from adriamycin
cytotoxicity in vitro.
Methods. Adriamycin cytotoxicity was assessed in MG-63 osteoblast-like
and PC-3 prostate cancer monolayer and three-dimensional collagen
coculture systems using the DNA content and trypan blue exclusion
assays, analysis of indexes of cell cycle by flow cytometry,
determination of DNA fragmentation on simple agarose gel and terminal
deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay,
and immunocytochemistry.
Results. Adriamycin (100 nM) arrested both the PC-3 and MG-65 cells at
the G2/M phase in the cell cycle but induced apoptosis only in PC-3
cells, as assessed by flow cytometry, trypan blue exclusion, and agarose
gel. Optimal doses of MC-63 CM (50 mu g/mL), insulin-like growth factor
I (50 ng/mL), and transforming growth factor-beta-1 (25 ng/mL), as
determined by DNA content assay, partially neutralized the adriamycin
cytotoxicity of PC-3 cells detected by flow cytometry and trypan blue
exclusion. In addition, MC-63 cells rescued PC-3 cells from adriamycin
apoptosis in the three-dimensional type I collagen gel coculture system,
as analyzed by TUNEL assay.
Conclusions. These data suggest that osteoblast-like cells and
osteoblast-derived growth factors can optimize survival of metastatic
prostate cancer cells, thereby helping to develop cytotoxic
drug-resistant growth in vitro. UROLOGY 52: 341-547, 1998. (C) 1998,
Elsevier Science Inc. All rights reserved.
Συγγραφείς:
Reyes-Moreno, C
Sourla, A
Choki, I
Doillon, C and
Koutsilieris, M
