Pterostilbene upregulates MICA/B via the PI3K/AKT signaling pathway to enhance the capability of natural killer cells to kill cervical cancer cells

Abstract

Abstract Natural killer (NK) cells are the main effector of the innate immune response of cells undergoing a malignant transformation in cancer microenvironment. NK cells recognize their targets through a complex array of activating and inhibitory receptors, which regulate the intensity of the effector response against individual target cells. However, many studies have shown that the shortage of the major histocompatibility complex class I chain-related proteins A and B(MICA/B) on the surface of cancer cells can evade the recognition of immune cells and produce resistance to NK cell killing. Through consulting the database and molecular docking, it was found that pterostilbene (PTS;3,5-dimethoxy-40-hydroxystilbene) in blueberry extract may inhibit PI3K/AKT signaling pathway and up-regulate the expression of the MICA/B in cervical cancer. MTT assay, flow cytometry, colony formation assay and viability/cytotoxicity assay evaluated the effects of PTS on cervical cancer cell proliferation and apoptosis. The results of western blot and quantitative real-time polymerase chain reaction (qRT-PCR) further confirmed that PTS could regulate the cytolytic activity of NK cells to cancer cells by up-regulating the expression of MICA/B, and modulate the anti-cancer immune response in cervical cancer.