Ginsenoside Re Suppresses Tumorigenesis in NSCLC through PERKMediated Endoplasmic Reticulum Stress and the Mitochondrial Apoptosis Pathway

INTRODUCTION: To investigate the antitumor effects of ginsenoside Re on human non-small cell lung cancer cells, specifically the NCI-H460 and 95D cell lines. METHODS: This study investigated the effects of ginsenoside Re on the proliferation of two cell lines using the CCK-8 assay; observed changes in cell morphology using DAPI and AO/EB staining; analyzed cell cycle and apoptosis rate using flow cytometry; and evaluated cell migration and invasion ability using Transwell and wound healing assays. Western blotting and qPCR results indicated that ginsenoside Re induces apoptosis in NCI-H460 and 95D cells by regulating the expression of genes and proteins, including Bax, BIP, CHOP, eIF-2α, Bcl-2, and β-actin. RESULTS: Ginsenoside Re inhibited the proliferation of two cell types in a time- and dosedependent manner. Cell cycle analysis revealed that ginsenoside Re induced G2 phase arrest in NCI-H460 cells and G1/S phase arrest in 95D cells, and that the morphology of apoptosis could be visualized by DAPI and AO/EB fluorescence staining. Cell scratchhealing and invasion assays confirmed that ginsenoside Re inhibited the invasion and migration of NCI-H460 and 95D cells, and the coverage of 95D cells decreased from 73.17±0.26% to 33.02±0.40%. DISCUSSION: Ginsenoside Re significantly inhibited NSCLC 95D and NCI-H460 cells by suppressing proliferation, cell cycle progression, migration, invasion, and inducing apoptosis. CONCLUSION: Ginsenoside Re can effectively induce tumor cell apoptosis by regulating the endoplasmic reticulum apoptosis pathway and thereby exert anti-tumor effects. The experiment provides a reliable basis for establishing a mechanistic framework explaining the role of ginsenoside Re in non-small cell lung cancer.