This study tested hypoxia-inducible factor 1-α (HIF-1α) in lung cancer patients and analyzed the microRNA-15a (miR-15a) expression in A549 cells under different local hypoxia microenvironments.
Expression changes of E6 and E7 significantly promoted the protein expression of HIF-1α, the expression of both protein and mRNA of GLUT1, but had no effect on the expression of HIF-1α mRNA in lung cancer cells.
To compare iodine content (IC) of solitary lung cancer using dynamic measurements of CT attenuation (Hounsfield Units, HU) and to correlate their quantitative CT data with expressions of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and hypoxia-inducible factor-1α (HIF-1α) using immunostaining methods.
Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes.
These findings highlight the pivotal role of the FOXO3a/miR-622 axis in inhibiting HIF-1α to interfere with tumor metastasis, and this information may contribute to development of novel therapeutic strategies for treating aggressive lung cancer.
In the stratified analysis, significant associations were found between the Hif-1/HIF-11790G/A polymorphism and lung cancer, pancreatic cancer and oral squamous cell carcinoma.
The high-throughput screening led to the identification of a class of aminoalkyl-substituted compounds that inhibited hypoxia-induced HIF-1 target gene expression in human lung cancer cell lines at low nanomolar concentrations.
These results suggest that exposure to nicotine could mimic effects of hypoxia to stimulate HIF-1α accumulation and activity that might underlie the high metastatic potential of lung cancer.
Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were observed for individuals with HIF-1α-1772 T/T genotype against CC/CT genotypes (an OR of 4.04, 95% confidence interval [CI] = 2.02-8.08, P = 0.0001), and HIF-1α-1790 A/A genotype against GG/GA genotypes (an OR of 4.42, 95% CI 2.22-8.78, P < 0.0001).
In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na+-K+ ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues.
These results provide a strong rationale to target Hsp90 as a means to block radiation-induced HIF-1alpha and thus to circumvent radioresistance in lung cancer cells.
Then, we investigated whether hypoxia induce the expression of CCR7 through HIF-1alpha and/or HIF-2alpha and observed the effects of upregulated CCR7 on the migration and invasion of lung cancer cells.
We conclude that (i) HIF-1alpha overexpression enhances lung cancer cell invasion at least through up-regulating the expression and activities of uPAR, MMP1, and MMP2; and (ii) induction of MMP1 participates in cell invasion and also plays an important role in HIF-1alpha-induced activation of MMP2.