Action of Hexachlorobenzene on MDA-MB-231 human breast cancer cell invasion and tumour growth

CAROLINA PONTILLO; PAOLA ROJAS; FLORENCIA CHIAPPINI; CLARA VENTURA; CLAUDIA COCCA; CLAUDIA LANARI; DIANA KLEIMAN DE PISAREV; ANDREA RANDI

Paris

Congreso; 47th Congress of the European Societies of Toxicology EUROTOX; 2011

Sociedades Europeas de Toxicologia

Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound. We demonstrated that HCB stimulates cell migration of MDA-MB-231 breast cancer cells via c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways. Increased activity of metalloprotease-9 (MMP-9) is involved in angiogenesis, invasion, and metastasis. Our aim was to examine HCB action on cell invasion and MMP-9 activity in vitro, and tumor growth and metastasis in vivo. Cells were exposed to HCB (0, 0.005, 0.05, 0.5 and 5 ìM) for 24 hours and then, cell invasion (matrigel coated transwells) and MMP-9 activity (gelatine zymography) were assayed. To analyse tumour growth and spontaneous metastasis, MDA-MB-231 cells (6x106) were injected s.c. into both flanks of female athymic nude mice. After 10 days, HCB (0.3, 3, 30 mg/kg) or vehicle were administered i.p. into nude mice and tumours were measured. Animals were sacrificed at 30 days after treatment and lung, liver and thoracic lymph node tissues were processed for histological analysis. HCB in vitro significantly increased cell invasion (117%,p<0.05) at 5 ìM and MMP-9 activity at 0.05, 0.5 and 5 ìM (15%, 42% and 40%,p<0.001). In the mouse xenograft assay, HCB (0.3 and 3 mg/kg) increased tumour volume (3244% and 3093%,p<0.001) and tumour weight (1230%,p<0.05). Lung, liver and lymph node metastases were registered in few control and treated mice, however the increase induced by HCB was not statistically significant. Our data indicate that HCB promotes MDA-MB-231 breast cancer growth in vivo and invasion and MMP-9 activity in vitro. More experiments are necessary to prove the prometastatic effect of HCB in xenografts.