| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 93 === Tumor hypoxia has been reported to promote tumor growth and metastasis via angiogenesis in vitro. In the present study, the effect of hypoxia on tumor growth was studied in vivo. Adult BALB/c male mice were used and murine CT26 colon adenocarcinoma cells were implanted subcutaneously. After implantation, mice were divided into three groups: normoxia (N), normobaric hypoxia (NH, 760 mmHg, PO2=76 mmHg, 10 hrs/day), and hypobaric hypoxia (HH, 380 mmHg, PO2=76 mmHg, 144 hrs/week) for 21 days. After hypoxic treatment, the order of increase of hematocrit was as fallow: HH >> NH >> N. No difference in averaged body weight was observed between N mice and NH mice. However, the averaged body weight of HH mice was significantly lower than that of normoxic mice. The averaged tumor volume of NH mice was slightly but insignificantly larger than that of N mice. Nevertheless, the averaged tumor volume of HH mice was smaller than normoxic mice. Hypoxia inducible factor (HIF)-1���n�nwas elevated in the tumors of hypoxic mice (NH and HH) at 14 days after implantation. Furthermore, hypoxic treatments (NH and HH) elevated VEGF mRNA and protein expression in tumors but showed no changes in serum VEGF level. A strong immunoreactivity of CD-31, an indicator of endothelial cells, was found in the tumor of hypoxic mice (NH and HH) at day 21, indicating a hypoxia-induced augmentation of angiogenesis. Moreover, NFκB binding activity was significantly increased in the tumor of hypoxic mice (NH and HH). In addition, hypoxic treatments (NH and HH) increased the COX II protein expression, mdr1 mRNA, thymidylate synthase mRNA in tumors. However, hypoxic treatments differentially altered serum IL-6 level. IL-6 in NH group was higher than that of N group, while IL-6 in HH group was lower than that of N group . There was no difference in Hsp70 and Hsp60 levels in tumors from these three groups.
Our in vivo data demonstrated that HH reduced tumors of hypoxic characteristics. One of the possibilities may be due to the deteriorated environment under HH. On the other hand, our in vivo study show that tumors in mice subjected to NH express tumor hypoxic characteristics, including a small increase in tumor size, elevation in HIF-1��, VEGF and angiogenesis, indicating establishment of hypoxic condition of tumor cells in vivo. Furthermore, NFκB activation and IL-6, COXII may be involved in normobaric hypoxia-induced angiogenesis and tumor growth in vivo. Therefore, the effect of NH on tumor growth is more pathophysiologically relevant.
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