Hypoxia, which is commonly observed in many solid
tumors, is a major impediment to chemo- or
radiation therapy.
Hypoxia is also known to overexpress/activate
signal transducer and activator of transcription 3 (STAT3) leading to
tumor progression as well as drug resistance. We hypothesized that increased oxygenation of the hypoxic
tumor may have an inhibitory effect on STAT3 activation and hence
tumor-growth inhibition. Mice containing human
ovarian cancer xenograft
tumor were exposed to hyperbaric
oxygen (HBO; 100%
oxygen; 2 atm; 90-min duration) daily, for up to 21 days. Mice exposed to HBO showed a significant reduction in
tumor volume, with no effect on
body weight. STAT3 (Tyr 705) activation and cyclin-D1
protein/
mRNA levels were significantly decreased up on HBO exposure. Interestingly, HBO exposure, in combination with weekly administration of
cisplatin, also significantly reduced the
tumor volume; however, this group of mice had drastically reduced
body weight when compared to other groups. While conventional wisdom might suggest that increased oxygenation of
tumors would promote
tumor growth, the results of the present study indicated otherwise.
Hyperoxia appears to inhibit STAT3 activation, which is a key step in the ovarian
tumor progression. The study may have important implications for the treatment of
ovarian cancer in the clinic.