Carbon dioxide, Hypoxia and Low pH Lead to Overexpression of c-myc and HMGB-1 Oncogenes in Neuroblastoma Cells

Abstract

Purpose: It has been reported that CO₂ gas, used to establish a pneumoperitoneum during laparoscopy, affects the behavior of tumor cells. The proto-oncogenes c-myc and HMGB-1 mediate aggressive behavior of neuroblastomas. We studied whether exposure to CO₂, hypoxia or acidosis affects the expression of c-myc and HMGB-1 in neuroblastoma cells.

Methods: SH-SY5Y cells were incubated with 100% CO₂, 95% helium/5% CO₂ or pH 6.2 for 2 h. The expression of c-myc and HMGB-1 was measured by Western blot test immediately, 3 h and 6 h after incubation. Additionally, we measured apoptosis after incubation using fluorometric measurements of caspase 3 and 7 activity.

Results: C-myc (160±26%, p=0.007 and 138±16% vs. control, p=0.04) and HMGB-1 proteins (140±13% and 136±11%, both p=0.037) were found to be significantly upregulated 6 h after incubation with CO₂ and helium. There was early upregulation of both oncogenes 3 h after CO₂ incubation (251±79%, p=0.04 and 292±136, p=0.037). Correspondingly, pH 6.2 led to significant overexpression. Levels of apoptosis were reduced.

Conclusions: Exposures mimicking conditions of CO₂ pneumoperitoneum lead to significant overexpression of c-myc and HMGB-1 in neuroblastoma cells with decreased apoptosis. These results point to a negative influence and potentially increased malignancy of tumor cells.

Key words

neuroblastoma - carbon dioxide - oncogenes

References

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