β₂肾上腺素受体通过HIF-1α调控NNK诱导的胰腺癌细胞进展

Objective: To explore the mechanism of β₂-adrenogenic receptor mediating the progression of NNK-induced pancreatic cancer cells. Methods: Pancreatic cancer cell lines (MIA PaCa-2 and BxPC-3) were incubated with NNK. ShRNA targeting HIF-1α was applied to knockdown HIF-1α expression. ICI 118551 was used to inhibit β₂-adrenogenic receptor signaling. Invasion of MIA PaCa-2 and BxPC-3 cells was detected by Transwell assay. The protein expressions of HIF-1α, Cyclin D1 and VEGF were determined by Western blot. Cell cycle was determined by flow cytometric analysis. Results: NNK could significantly upregulate HIF-1α expression in MIA PaCa-2 and BxPC-3 cells and increase the invasion and proliferation of pancreatic cancer cells. However, ICI 118551 or sh-HIF-1α could reverse the effect of NNK on MIA PaCa-2 and BxPC-3 cells. Furthermore, when HIF-1α expression was upregulated by CoCl₂, the inhibitory effect of ICI 118551 on NNK was reversed, with a prominent increase in pancreatic cancer cell invasion. Conclusion: β₂-adrenogenic receptor mediates the invasion and proliferation of NNK-induced pancreatic cancer cells through HIF-1α.