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

C A PONTILLO; P ROJAS; F CHIAPINI ; C VENTURA; C COCCA; C LANARI; D KLEIMAN; A RANDI

Paris

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

EUROTOX

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. We examined 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 Micromolar) for 24 h 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 (6×106) were injected s.c. into both flanks of female athymic nude mice. After 10 days, HCB (0.3, 3, 30 mg/kg) or vehicle was 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 lower than 0.05) at 5 Micromolar and MMP-9 activity at 0.05, 0.5 and 5 Micromolar 15%, 42% and 40%, p lower than 0.001). In the mouse xenograft assay, HCB (0.3 and 3mg/kg) increased tumour volume (3244% and 3093%, p lower than 0.001) and tumour weight (1230%, p lower than 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.