In vivo real-time monitoring of the development of hypoxia and angiogenesis in cervical cancer

Abstract

The growth of solid tumors is inevitably accompanied by hypoxia and angiogenesis. Understanding the true state of tissue hypoxia and angiogenesis during tumor progression will help further comprehend the tumor microenvironment and cancer therapy. Here, we provided a novel strategy for the long-term tracking of tumor hypoxia and angiogenesis in cervical cancer. The hypoxia response elements (HRE)-driven luciferase (LUC) reporter gene transfected cervical cancer cell lines were constructed for hypoxia visualization. The hypoxia response activity of HRE-driven LUC was verified in HeLa cells and then monitored via the HeLa-HRE-LUC tumor-bearing mouse models by bioluminescence imaging (BLI). An oxygen-sensitive nanoparticle was constructed for glycerol monooleate cubic liquid crystal material loaded with Ir(piq)3/IR780 and could be used for phosphorescence-fluorescence imaging. The imaging result showed that the nanoparticles labeled the low oxygen region overlapped with the BLI signal region detected by HRE-driven LUC in vivo, which confirmed that the hypoxia visualization platform could genuinely reflect the hypoxia level in vivo. The angiogenesis in vivo was reflected by changes in deoxygenated/oxygenated hemoglobin detected by photoacoustic imaging. Besides these, anticancer drug apigenin down-regulated HIF-1α and VEGF under hypoxia conditions and inhibited the tube formation in vitro. Then, the inhibition effects were verified in the hypoxia and angiogenesis visualization model in vivo. This study confirmed a novel in vivo real-time monitoring of tumor hypoxia and angiogenesis strategy, which can provide useful information for further research on cancer progression and anticancer therapy.