The ablative role of minimally invasive surgery (MIS) in neuroblastoma (NB) is still controversial due to the possible CO₂ pneumoperitoneum side-effects on tumor aggressiveness. It is known that CO₂ produces hypoxic condition with changes in tumor microenvironment influencing cell functions. Here we investigated whether CO₂ exposure affects the transcription factor HIF-1α and the apoptotic signalling pathway in SH-SY5Y NB cells. SH-SY5Y cells were exposed to a pressure of 15 mmHg CO₂ (100%) for 4 h (T0) and then moved to normal condition for 24 h (T₂₄). In control and CO₂ -exposed cells, we analyzed the mRNA levels and DNA binding activity of HIF-1α. We also evaluated the proliferative activity and cell viability as well as caspase-9/3 cleavage and nuclear fragmentation. A significant increase in HIF- 1α activation was observed in SH-SY5Y cells exposed to CO₂ compared to control cells. CO₂ treatment also decreased the proliferation rate and the percentage of viable cells. In addition, the expression and cleavage of caspase-9 and -3 were significantly increased in NB cells exposed to CO₂. These data correlated with apoptotic feature observed in CO₂ -treated NB cells. Our findings show that CO₂ -induced hypoxic condition exerts cytotoxic effects on NB cells by eliciting mitochondrial apoptotic pathway and thereby improving the understanding of the possible clinical impact of CO₂ pneumoperitoneum on NB behaviour.

CO(2) pneumoperitoneum induces in vitro hypoxic response culminating in apoptosis of human neuroblastoma cells

CURRO', MONICA;MONTALTO, ANGELA SIMONA;Impellizzeri, Pietro;MONTALTO, ERIKA;RISITANO, ROBERTO;RUSSO, TIZIANA;CHIRICO, VALERIA;ARRIGO, Teresa;SALPIETRO DAMIANO, Carmelo;ROMEO, Carmelo;IENTILE, Riccardo
2014

Abstract

The ablative role of minimally invasive surgery (MIS) in neuroblastoma (NB) is still controversial due to the possible CO₂ pneumoperitoneum side-effects on tumor aggressiveness. It is known that CO₂ produces hypoxic condition with changes in tumor microenvironment influencing cell functions. Here we investigated whether CO₂ exposure affects the transcription factor HIF-1α and the apoptotic signalling pathway in SH-SY5Y NB cells. SH-SY5Y cells were exposed to a pressure of 15 mmHg CO₂ (100%) for 4 h (T0) and then moved to normal condition for 24 h (T₂₄). In control and CO₂ -exposed cells, we analyzed the mRNA levels and DNA binding activity of HIF-1α. We also evaluated the proliferative activity and cell viability as well as caspase-9/3 cleavage and nuclear fragmentation. A significant increase in HIF- 1α activation was observed in SH-SY5Y cells exposed to CO₂ compared to control cells. CO₂ treatment also decreased the proliferation rate and the percentage of viable cells. In addition, the expression and cleavage of caspase-9 and -3 were significantly increased in NB cells exposed to CO₂. These data correlated with apoptotic feature observed in CO₂ -treated NB cells. Our findings show that CO₂ -induced hypoxic condition exerts cytotoxic effects on NB cells by eliciting mitochondrial apoptotic pathway and thereby improving the understanding of the possible clinical impact of CO₂ pneumoperitoneum on NB behaviour.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3090961
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