Volume 49 Number 3

Imperatorin alleviates cancer cell viability by suppressing M2 macrophage polarization through Nox2-ROS signaling pathway

Suyun Yong^a, Jianhua Wang^b, Nan Zhou^a,*, Peng Zhang^a

 
ABSTRACT:     The tumor microenvironment (TME) plays a crucial role in regulating tumor progression. Tumor associated macrophages, as prominent cellular components of the tumor microenvironment, exhibit high plasticity and can either promote or suppress tumor development. Imperatorin, a natural coumarin derivative with diverse pharmacological activities, has been reported to inhibit vascular remodeling and cancer progression. In this study, we aimed to explore the potential mechanisms by which imperatorin regulates TME in colon cancer cells. A co-culture model of macrophages with colon cancer HT-29 and LoVo cells was established and treated with imperatorin. CCK-8 assay was used to measure cell viability. M2 macrophage surface markers were determined by immunohistochemistry and enzyme-linked immunosorbent assay. ROS level was measured through Dihydroethidium fluorescent probe assay. The mRNA and protein expression of nicotinamide adenine dinucleotide phosphate oxidase were detected by RT-PCR and Western blot analysis. Treatment with imperatorin effectively decreased the viability of the colon cancer HT-29 and LoVo cells, inhibited the cytokine CSF-1 which induced upregulation of CD163 and CD206 in macrophages, and reduced the expression of M2 macrophage phenotype markers and the Nox2/ROS/AMPK/STAT3 signaling pathway. These results suggest that imperatorin inhibits M2 macrophage polarization and attenuates the viability of colon cancer HT-29 and LoVo cells by downregulating the expression of the Nox2/ROS/AMPK/STAT3 signaling pathway.

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* Corresponding author, E-mail: zhounansx2024@163.com

Received 28 May 2025, Accepted 3 Dec 2025