Restoration of IGFBP-rP1 increases radiosensitivity and chemosensitivity in hormone-refractory human prostate cancer.

Abstract

We previously reported the tumor-suppressive activity of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) through induction of apoptosis in human prostate cancer cells. The aim of this study was to investigate the effects of IGFBP-rP1 for radiosensitivity and chemosensitivity in hormone-refractory human prostate PC-3 cancer cells. Five assays were performed using PC-3 cells transfected with IGFBP-rP1 (PC-3rP1) and control cells transfected with an empty vector (PC-3N): PC-3rP1 and PC-3N were compared by clonogenic survival assay, cell cycle analysis and apoptotic assay for radiosensitivity. The number of colonies of PC-3rP1 cells significantly decreased after 4 and 8 Gy of irradiation, compared with those of PC-3N in the clonogenic survival assay. After 16 hr irradiation at 8 Gy, the percentage of apoptotic cells significantly increased in PC-3rP1 compared with PC-3N. Growth of PC-3rP1 was significantly lower than that of PC-3N after docetaxel treatment both in vitro and in vivo. These results indicate that restoration of IGFBP-rP1 to PC-3 cells increases both their radiosensitivity and chemosensitivity.

• Authors: Mitsuhiro Seki, Jun Teishima, Hideki Mochizuki, Kazuaki Mutaguchi, Hiroaki Yasumoto, Kiyotaka Oka, Hirotaka Nagamatsu, Koichi Shoji, Akio Matsubara
• Journal: Hiroshima journal of medical sciences (Hiroshima J Med Sci) Vol. 62 Issue 1 Pg. 13-9 (Mar 2013) ISSN: 0018-2052 [Print] Japan
• PMID: 23600329 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Insulin-Like Growth Factor Binding Proteins
• Taxoids
• insulin-like growth factor binding protein-related protein 1
• Docetaxel

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, radiation effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects, radiation effects)
• Cell Survival (drug effects, radiation effects)
• Docetaxel
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Drug Resistance, Neoplasm
• G2 Phase Cell Cycle Checkpoints (drug effects, radiation effects)
• Humans
• Insulin-Like Growth Factor Binding Proteins (genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Prostatic Neoplasms (drug therapy, genetics, metabolism, pathology, radiotherapy)
• Taxoids (pharmacology)
• Time Factors
• Transfection
• Tumor Burden (drug effects, radiation effects)
• Xenograft Model Antitumor Assays