Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor

Background Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1 alpha in MPNSTs is unclear. Methods The expression of HIF-1 alpha was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1 alpha-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1 alpha. Results The nuclear expression of HIF-1 alpha was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1a was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P <= 0.0001) analyses. HIF-1 alpha knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1 alpha, effectively inhibited the growth of MPNST cells and induced their apoptosis. Conclusion Inhibition of HIF-1 alpha signaling is a potential treatment option for MPNSTs.