Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents.

摘要: Scatter factor (SF) (hepatocyte growth factor) is a cytokine that may play role in human breast cancer invasiveness and angiogenesis. We now report SF can block the induction of apoptosis by various DNA damaging-agents, including cytotoxic agents used therapy. protected MDA-MB-453 cells, EMT6 mouse mammary tumor cells MDCK renal epithelial against induced adriamycin (ADR), X-rays, ultraviolet radiation, other agents. Protection was observed assays fragmentation, cell viability (MTT), clonogenic survival. ADR dose- time-dependent; maximal protection required pre-incubation with 75-100 ng/ml for 48 h or more. functional receptor (c-Met), but not dependent on p53. Western blotting analysis revealed pre-treatment inhibited ADR-induced decreases levels Bcl-XL, an anti-apoptotic protein related to Bcl-2; dose-response time course characteristics SF-mediated increases Bcl-XL ADR-treated were consistent degrees under same conditions. Furthermore, down-regulated MDA-MB-231 finding failed protect these ADR, despite fact they contain c-Met receptor. In contrast blocked c-Myc expression p21WAF1/CIP1 BRCA1 cells. However, did cause significant changes cycle distribution These findings suggest involve inhibition one more pathways activation particularly target mitochondrial membrane pore-forming as component protective mechanism. By implication, accumulation within cancers contribute development radio- chemoresistant phenotype.