Figure 3.

Intermittent hypoxia (IH) promotes endothelial cell proliferation through upregulation of vascular endothelial growth factor (VEGF) expression and ultimately accelerates lung cancer progression. (A) Comparison of tumor size in each group. (i) The tumor size of lung cancer in the IH group was larger than that in the control (CTL) group. Endostatin (ED) inhibits the proliferation of endothelial cells (CTL+ED, IH+ED) and slows tumor growth. (ii) After 15 and 30 days of exposure to IH, 18F-FDG PET demonstrated tumor size. Endothelial cells were the target of ED treatment, and lung cancer proliferation is inhibited by ED. Yellow arrows point to tumors (80). (B) In contrast to room air (RA), chronic intermittent hypoxia (CIH) promotes lung cancer proliferation by inducing neovascularization. (i) The number and volume of tumors are larger in the CIH group. (ii) The effect of CIH on the neovascularization of lung cancer. Representative immunohistochemistry images (left: Ki-67 and right: CD31) (magnification, ×200). (iii) Hypoxia-inducible factor-1a (HIF-1α) and VEGF expression levels in the CIH group are higher than those in the RA group (81). Reprinted with permission from Ref (80, 81).