Department of Pharmacy Experimental Teaching Center of Pharmaceutical College, Inner Mongolia Medical University, Hohhot, China.
Inner Mongolia Research Center for Drug Screening, Hohhot, China.
BMC Pharmacol Toxicol. 2022 Apr 26;23(1):26. doi: 10.1186/s40360-022-00564-8.
The main causes of lung cancer are smoking, environmental pollution and genetic susceptibility. It is an indisputable fact that PAHs are related to lung cancer, and benzo(a) pyrene is a representative of PAHs. The purpose of the current investigation was to investigate the interaction between AhR and HIF-1 signaling pathways in A549 cells, which provide some experimental basis for scientists to find drugs that block AhR and HIF-1 signaling pathway to prevent and treat cancer.
This project adopts the CYP1A1 signaling pathways and the expression of CYP1B1 is expressed as a measure of AhR strength index. The expression of VEGF and CAIX volume as a measure of the strength of the signal path HIF-1 indicators. Through the construction of plasmid vector, fluorescence resonance energy transfer, real-time quantitative PCR, western blotting and immunoprecipitation, the interaction between AhR signaling pathway and HIF-1 signaling pathway was observed.
BaP can enhance the binding ability of HIF-1α protein to HIF-1β/ARNT in a dose-dependent manner without CoCl. However, the binding ability of AhR protein to HIF-1β/ARNT is inhibited by HIF-1α signaling pathway in a dose-dependent manner with CoCl.
It is shown that activation of the AhR signaling pathway does not inhibit the HIF-1α signaling pathway, but activation of the HIF-1α signaling pathway inhibits the AhR signaling pathway.
肺癌的主要病因是吸烟、环境污染和遗传易感性。多环芳烃（PAHs）与肺癌有关，苯并[a]芘是 PAHs 的代表，这是一个不争的事实。本研究的目的是探讨 A549 细胞中 AhR 和 HIF-1 信号通路之间的相互作用，为科学家寻找阻断 AhR 和 HIF-1 信号通路的药物以预防和治疗癌症提供一些实验依据。
本项目采用 CYP1A1 信号通路，以 CYP1B1 的表达作为 AhR 强度指标，用 VEGF 和 CAIX 的表达作为 HIF-1 信号通路强度指标。通过构建质粒载体、荧光共振能量转移、实时定量 PCR、western blot 和免疫沉淀，观察 AhR 信号通路与 HIF-1 信号通路的相互作用。
BaP 可在无 CoCl2 存在的情况下，剂量依赖性增强 HIF-1α 蛋白与 HIF-1β/ARNT 的结合能力。然而，HIF-1α 信号通路在 CoCl2 存在的情况下，剂量依赖性地抑制 AhR 蛋白与 HIF-1β/ARNT 的结合能力。
实验结果表明，AhR 信号通路的激活并不抑制 HIF-1α 信号通路，而是 HIF-1α 信号通路的激活抑制 AhR 信号通路。
