过氧化氢诱导多细胞前列腺肿瘤球体中c-fos表达及生长刺激的钙依赖性

Calcium-dependence of hydrogen peroxide-induced c-fos expression and growth stimulation of multicellular prostate tumor spheroids.

作者信息

Sauer H, Diedershagen H, Hescheler J, Wartenberg M

机构信息

Institute for Neurophysiologie, University of Cologne, Germany.

出版信息

FEBS Lett. 1997 Dec 15;419(2-3):201-5. doi: 10.1016/s0014-5793(97)01456-7.

DOI:10.1016/s0014-5793(97)01456-7

PMID:9428634

Abstract

Hydrogen peroxide (H2O2) in nanomolar concentrations (20-100 nM) stimulated the growth of small (diameter 100 +/- 30 microm) multicellular prostate cancer spheroids and increased c-fos expression. H2O2 transiently raised [Ca2+]i by Ca2+ release from intracellular stores as the transient persisted in low (10 nM) Ca2+ solution but was abolished when intracellular Ca2+ stores were depleted by thapsigargin or chelation of [Ca2+]i with BAPTA. The H2O2-induced [Ca2+]i transient was furthermore inhibited by the P2-purinoreceptor antagonists suramin and basilen blue, indicating that H2O2 may act via purinergic receptor stimulation. Treatment of spheroids with either suramin, basilen blue or BAPTA inhibited the H2O2-induced growth stimulation and c-fos expression, indicating that the H2O2-mediated growth stimulation of multicellular spheroids is mediated via a Ca2+-dependent pathway.

摘要

纳摩尔浓度（20 - 100 nM）的过氧化氢（H2O2）刺激了小的（直径100 ± 30微米）多细胞前列腺癌球体的生长，并增加了c-fos表达。H2O2通过从细胞内储存库释放Ca2+短暂升高[Ca2+]i，因为该瞬变在低（10 nM）Ca2+溶液中持续存在，但当细胞内Ca2+储存库被毒胡萝卜素耗尽或[Ca2+]i被BAPTA螯合时被消除。此外，H2O2诱导的[Ca2+]i瞬变被P2-嘌呤受体拮抗剂苏拉明和巴西蓝抑制，表明H2O2可能通过嘌呤能受体刺激起作用。用苏拉明、巴西蓝或BAPTA处理球体抑制了H2O2诱导的生长刺激和c-fos表达，表明H2O2介导的多细胞球体生长刺激是通过Ca2+依赖性途径介导的。