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Ginsenoside Rh2 (G-Rh2), a component of ginseng extraction, exerted anti-tumor property in the occurrence and progress of human tumors. Vestibular schwannoma (VS) is a kind of benign tumor. Extraction of traditional Chinese herb has been applied to treat VS as adjuvant therapy. Nevertheless, G-Rh2-related molecular mechanisms in VS progress are not yet clear. The purpose of current study is to unveil the function and potential molecular mechanism of Rh2 in VS cellular functions. At first, the viability and apoptosis of VS cells treated with different concentrations of Rh2 were assessed. Autophagy and DNA damage response can be induced by multiple drugs. Here, we observed the changes of autophagy and DNA damage in Rh2-induced VS cells. Based on the experimental data, treatment with Rh2 contributed to cell apoptosis by inducing DNA damage and suppressing DNA damage. LAMP2 (lysosomal associated membrane protein 2), an autophagy inducer, was downregulated in Rh2-treated VS cells. Through mechanism study, we determined that Rh2 led to the transcriptional inactivation of LAMP2 by downregulating its transcription activator NR2F2 (nuclear receptor subfamily 2 group F member 2). In addition, NR2F2 overexpression recovered the role of Rh2 in cell functions, which was further rescued by the silence of LAMP2. Collectively, our study unveiled a novel NR2F2/LAMP2 axis in Rh2-mediated VS cells, which potentially contributes to the therapy for VS. Image 1 • Rh2 induced apoptosis of primary VS cells by regulating DNA damage and autophagy. • LAMP2 was downregulated in Rh2-induced primary VS cells and its recovery attenuated Rh2-mediated cellular functions. • NR2F2 positively regulated LAMP2 expression through transcriptional activation. • NR2F2/LAMP3 axis regulated Rh2-mediated functions of primary VS cells. [ABSTRACT FROM AUTHOR]

Abstract Recent clinical researches demonstrated "obesity paradox" in chronic obstructive pulmonary disease (COPD) patients. However, why obesity is beneficial to COPD development remains unclear. Obesity is distinguished by hyperinsulinemia, and cellular senescence of airway epithelial cells (AEC) is involved in COPD progression. In this study, we aim to investigate the roles of insulin in high concentration in AEC cellular senescence. Human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (HSAEpiC) were used for experiments and treated with insulin in indicated time period and concentration with or without 1% cigarette smoke extract (CSE) exposure, and autophagy activator (rapamycin) or inhibitor (chloroquine) after exposed to 1% CSE. The expression of senescence protein (p21), cell cycle related protein (cyclinE), and autophagy protein (LC3B, Beclin-1 and p62) were determined by western blot. Cellular senescence was detected by Senescence-β-Galactosidase staining. Autophagy level was detected by GFP-LC3B fluorescent light. Results showed that insulin receded cellular senescence in different time and concentration, as indicated by decreased expression of p21, increased expression of cyclinE and down-regulated ratio of SA-β-Gal stained cells in BEAS-2B and HSAEpiC under physiological or CSE exposure condition. 5 μg/ml insulin treated for 48 h up-regulated the ratio of LC3B II/I, Beclin-1 and number of spot dots of GFP-LC3B, and down-regulated the level of p62 in AEC cells after 1% CSE exposure, while 1% CSE showed an opposite effect. Activating autophagy receded cellular senescence, and vice versa. Meanwhile, the effect of 5 μg/ml insulin on receding cellular senescence could be alleviated by autophagy inhibitor chloroquine or reinforced by autophagy activator rapamycin. In conclusion, insulin in high concentration could reduce the CSE induced cellular senescence of human airway epithelial cells through autophagy pathway. Highlights • Cellular senescence in human epithelial cells wasreducedby high concentration of insulinwith or without CSE exposure. • Autophagy was activated by high concentration of insulinin human epithelial cellsafter CSE exposure. • Cellular senescence was modulatedby autophagyin human epithelial cells. • Insulin could reduce cellular senescence in human epithelial cells though autophagy pathway. [ABSTRACT FROM AUTHOR]