Pictured left to right: T Billiar, D Geller
Wang R, Geller DA, Wink DA, Cheng B, Billiar TR. Nitric oxide and hepatocellular cancer. Br J Pharmacol. 2019 Aug 18. doi: 10.1111/bph.14838. Review. PubMed PMID: 31423564.
ABSTRACT
Nitric oxide (NO) has broad and sometimes dichotomous roles in cancer. The effects of NO in tumors depend on the type and localization of NOS isoforms, concentration and duration of NO exposure, and cellular sensitivity to NO. Hepatocellular cancer (HCC) is a common and lethal disease for which no effective therapy other than surgical resection exists. Over two decades of research has yielded evidence that NO generated by the inducible NO synthase (iNOS or NOS2) contributes to HCC progression in at least a subset of patients with HCC. The co-expression of iNOS with cyclooxygenase-2 (COX-2) may portend a particularly aggressive cancer phenotype in HCC and at the same time reveal an opportunity for pharmacologic intervention. In this review, we focus what is known about the influence of NO in HCC neoplastic transformation, proliferation and apoptosis, angiogenesis, invasion and metastasis, cancer stem cells, and the host immune response against the tumor. We discuss the implications of recent findings for targeting the NO pathways in HCC.
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