Ginsenoside Rk1 inhibits the malignant progression of lung cancer by inactivating the INSR/PI3K/AKT pathway

Abstract

Background

Lung cancer continues to be a primary contributor to global cancer deaths. The urgent need for effective therapeutic interventions has led researchers to explore natural compounds with potential anti-cancer properties. Ginsenoside Rk1 (Rk1), a pharmacologically active component derived from ginseng, has garnered attention for its reported anti-cancer effects, however, the molecular mechanisms underlying its action against lung cancer remain poorly elucidated.

Methods

This study employed a series of in vitro assays, including cell counting kit-8, cell colony formation, 5-Ethynyl-2’-deoxyuridine, flow cytometry, and Transwell assays, to assess the effects of Rk1 on lung cancer cell viability, proliferation, apoptosis, migration, and invasion. Western blotting, immunohistochemistry assay, and quantitative real-time polymerase chain reaction were used to evaluate the protein and mRNA expression, respectively. Bioinformatics tools such as Genecards, Swiss Target Prediction, and Cytoscape 3.9.1 were utilized for network pharmacological analysis and pathway mapping. The interaction between Rk1 and INSR was analyzed using a cellular thermal shift assay. Animal experiment was performed to validate the effect of Rk1 and INSR overexpression on the malignant progression of lung cancer cells.

Results

Rk1 treatment significantly inhibited lung cancer cell proliferation, migration, and invasion, while inducing cell apoptosis and autophagy. Importantly, we identified insulin receptor (INSR) as a pivotal target of Rk1. Notably, INSR expression was found to be upregulated in lung cancer tissues and cells. In addition, Rk1 treatment heat-stabilized INSR and reduced its protein expression in A549 cells. Depletion of INSR mimicked the inhibitory effects of Rk1, whereas overexpression of INSR mitigated these effects. Furthermore, Rk1 inactivated the PI3K/AKT pathway through the regulation of INSR. Further, INSR overexpression attenuated Rk1 treatment-induced inhibitory effect on the malignant progression of lung cancer cells.

Conclusion

This study provided novel insights into the molecular mechanisms by which Rk1 exerted its anti-cancer effects in lung cancer, specifically through targeting the INSR/PI3K/AKT pathway. These findings not only contributed to the understanding of Rk1’s therapeutic potential but also offered a rationale for its further development as a promising therapeutic agent for the treatment of lung cancer. The identification of INSR as a key target represents a significant advancement in the field, highlighting the importance of natural compounds in modern cancer therapy.