Astragalus Polysaccharide Eases G1 Phase-Correlative Bystander Effects through Mediation of TGF-βR/MAPK/ROS Signal Pathway After Carbon Ion Irradiation in BMSCs

Although Astragalus polysaccharide (APS) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of APS on the radiation-induced bystander effects (RIBE). The aim of this study was to investigate whether APS could suppress RIBE damage by inhibiting cell growth, micronucleus (MN) formation and 53BP1 foci number increased in bone marrow mesenchymal stem cells (BMSCs), named bystander cells, as well as to explore its mechanism. In this study, APS decreased proliferation and colony rate of bystander cells by inducing cell cycle arrest at G1 phase via extrinsic and intrinsic DNA damage. Regarding mechanism, APS inhibited mitogen-activated protein kinase (MAPK) signal pathway by down-regulating the expression of the key proteins, phosphorylated JNK (p-JNK), phosphorylated ERK (p-ERK) but not phosphorylated P38 (p-P38), and down-regulating their downstream function protein and molecule, cyclooxygenase-2 (COX-2) and reactive oxygen species (ROS). Moreover, in bystander cells, APS inhibits expression of transforming growth factor [Formula: see text] receptor II (TGF-[Formula: see text]R II), a cell membrane receptor, resulting in lower ROS production and secretion via TGF-[Formula: see text]R-JNK/ERK-COX-2/ROS not P38 signaling. They gave a hint that the decreased RIBE damage induced by APS treatment involved TGF-[Formula: see text]R-JNK/ERK-COX-2/ROS down-regulation.