Salidroside suppresses the multiple oncogenic activates and immune escape of lung adenocarcinoma through the circ_0009624‐mediated PD‐L1 pathway

Abstract

BackgroundLung adenocarcinoma (LUAD) is a fatal malignancy all over the world. Salidroside (SAL) is an active component extracted from Rhodiola rosea that has been reported to exert antitumor activity against several human cancers, containing lung adenocarcinoma (LUAD). The purpose of this study was to explore the effect and underlying mechanism of SAL in LUAD.MethodsCell viability, proliferation, migration, and invasion were measured using cell counting kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), and transwell assays. Effects of LUAD cells on the cytotoxicity, percentage, and death of CD8+ cells were detected using lactate dehydrogenase (LDH) and flow cytometry assays. Programmed cell death ligand 1 (PD‐L1) protein level was examined using western blot. Circ_0009624, enolase 1 (ENO1), and PD‐L1 levels were determined using real‐time quantitative polymerase chain reaction (RT‐qPCR). The biological role of SAL on LUAD tumor growth was assessed using the xenograft tumor model in vivo.ResultsSAL restrained LUAD cell proliferation, migration, invasion, and immune escape in vitro via modulating PD‐L1. Circ_0009624 expression was increased in LUAD. Applying SAL repressed circ_0009624 and PD‐L1 expression in LUAD cells. SAL treatment hindered suppressed various oncogenic activates and immune escape of LUAD cells by regulating the circ_0009624/PD‐L1 pathway. SAL blocked LUAD xenograft growth in vivo.ConclusionApplying SAL might constrain malignant phenotypes and immune escape of LUAD cells partially through the circ_0009624‐mediated PD‐L1 pathway, providing a novel insight for LUAD treatment.

A review of natural products targeting tumor immune microenvironments for the treatment of lung cancer

“…Salidroside promotes the immune activity of CD8+ T cells by inhibiting the expression of PD-L1, thereby preventing tumor immune escape in LUAD cells. However, the PD-L1 pathway mediated by circ_0009624 is the key to the above effect ( 153 ).…”