Abstract
Our previous study has demonstrated that 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd) enhanced radiation-induced inhibition of tumor growth through the apoptosis induction and the reduction of cell proliferation in colon26 solid tumor. In this study, we focused on hypoxic cell and examined the effects of ECyd on tumor cells in hypoxic condition both in vitro and in vivo.
Human gastric adenocarcinoma MKN45 cells in a gas-exchangeable chamber were exposed to hypoxic condition (oxygen concentration = 3 mmHg) by passing 100% N2 gas continuously. An increase in the accumulation of HIF-1α was observed when cells were incubated under hypoxia. However, HIF-1α expression was decreased to the level of normoxic condition when cells were incubated under hypoxia in the presence of 5 μM ECyd. In MKN45 xenograft, a significant reduction in tumor growth was observed in mice treated with a low dose of X-rays and ECyd compared with X-rays or ECyd alone. These results suggested that ECyd enhanced radiation-induced inhibition of tumor growth through the inhibition of hypoxia-induced expression of survival factors. The detailed mechanism of tumor suppression will be discussed.
