The effects of hypoxia induced Reactive oxygen species production in head & neck squamous cell carcinoma

• Main Authors: Lai yuan shu, 賴媛淑
• Other Authors: Kang BH
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/17215730600282312184

碩士 === 國防醫學院 === 海底醫學研究所 === 95 === Abstract Malignant tumor has been the leading causes of death in Taiwan for many years. Caner cells possess many special characteristics including rapid proliferation even in a hypoxia environment, a common feature found in the majority of human tumors resulting from tumors rapid growth and inadequate blood supply. Previous studies have showed that hypoxia causes the stability and activation of hypoxia inducible factor-1α(HIF-1α), which can induce the expression of vascular endothelia growth factor (VEGF). It is well known that VEGF plays an important role in angiogenesis and subsequently leads to tumors proliferation and invasion. In addition, HIF-1αalsoenhances the release of transforming growth factor-α(TGF-α) and binding and activation of epidermal growth factor receptor (EGFR). Several studies have demonstrated that activation of EGFR is associated with tumor cells proliferation and invasion. Another important finding is that the formation of reactive oxygen species (ROS) is also increased in response to hypoxia. Recently, many studies have reported that ROS can activate many transcriptional factors including HIF-1. Furthermore, ROS can induce the expression of VEGF, release of TGF-αand activation of EGFR in both tumor and non-tumor cells. These results suggest that the biological effects of ROS may be similar to that of HIF-1. Therefore, in the present study, we investigate the role of ROS induced by hypoxia on activation of HIF-1α VI and EGFR in head and neck tumor cells. Three tumor cells including FaDu, Detroit 562 and Scc25 were cultured in 1% O2 for different time period. The levels of superoxide anion (O2-) and hydrogen peroxide (H2O2) were measured by nitro blue tetrazolim (NBT) and 2,7-dichloridihydrofluorescein diacetate (DCFH-DA), respectively. The expression of HIF-1αand active form of EGFR was evaluated by Western blotting. Our results showed that incubation in hypoxia (1% O2 ) resulted in an increased formation of H2O2 but no significant difference of O2- production in all three types tumor cells compared with that of cells incubated in normoxia condition. Hypoxia also caused the induction of HIF-1αand EGFR in a time dependent manner. After hypoxia for 3 hrs, the H2O2 formation and HIF-1αexpression began to increase and reached the peak amount at hypoxia for 6 and 12 hrs, respectively. However, until hypoxia for 6 hrs the expression of active form of EGFR began to enhance and maintained for 24 hrs under hypoxia condition. Addition of catalase resulted in a significant inhibition of hypoxia-induced enhanced expression of HIF-1α and active form EGFR. These results showed that in head and neck tumor cells, hypoxia can increase H2O2 formation, which may play an important role in induction of HIF-1αand EGFR.