Journal of Clinical & Experimental Pharmacology

Abstract

Increasing Oxygen in Hypoxic Tumors

John L. Gainer and Miles F. Lankford

Background: Tumors are frequently hypoxic, affecting both chemotherapy and radiotherapy. Trans sodium crocetinate (TSC), a novel pharmaceutical agent, causes increases in oxygen levels of hypoxic tissues. It has also been shown, in animal models of cancer, that radiotherapy is more effective when used in conjunction with TSC. An increase in tumor oxygen should also affect the HIF-1? pathway. Thus, an in vitro study of that pathway in human glioblastoma cells was performed. Methods: This study involved the use of quantitative real time polymerase chain reaction technology and human glioblastoma multiforme cells. The cells were cultured under both hypoxic and normoxic conditions. Results: The inclusion of TSC in the media of the cells resulted in some genes in the HIF-1? pathway being either up- or down-regulated in a statistically-significant manner. These changes were opposite to those which occurred when the same cells were grown under hypoxic conditions but without TSC. In addition, those same genes reacted in an opposite manner when the cells were grown with TSC but under a normal oxygen environment. Conclusions: These results support previous observations that TSC reduces hypoxia in tumor cells. Since TSC caused statistical differences in gene expression under hypoxia different from those caused under normoxia, it suggests that there is not a direct effect of TSC on the HIF-1? pathway. Rather, TSC alters the gene expression due to a change in the response of the genes to different oxygen levels. These data also correlate with previous in vivo studies which show that TSC increases oxygen to hypoxic tissue but not to normal tissue. Thus, these data, combined with previous studies of animal cancer models, strongly suggest that TSC has the ability to increase cellular oxygen in tumor cells. Such a physiological change can be beneficial with combined with radiotherapy for cancer.