Lycorine Suppresses Non-Small-Cell Lung Cancer Progression Through Activating STING Pathway and Stimulating an...

Area of Science:

• Oncology
• Pharmacology
• Immunology

Background:

• Non-small-cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
• Lycorine (LYD), a sesquiterpene from medicinal plants, shows anti-cancer effects, but its NSCLC mechanisms are unclear.

Purpose of the Study:

• To elucidate the anti-tumor mechanisms of Lycorine (LYD) in non-small-cell lung cancer (NSCLC).
• To investigate LYD's effects on NSCLC proliferation, apoptosis, and immune modulation.

Main Methods:

• Assessed LYD's impact on NSCLC cell proliferation and apoptosis, measuring reactive oxygen species (ROS) levels.
• Utilized N-acetylcysteine (NAC) to block ROS and evaluated STING pathway activation and chemokine expression (CXCL10, CXCL9, CCL5).
• Examined LYD's effect on P70S6K and S6K protein levels and assessed in vivo anti-tumor activity in NSCLC mouse models.

Main Results:

• LYD significantly reduced NSCLC proliferation and induced apoptosis by increasing intracellular ROS.
• ROS inhibition by NAC reversed LYD's apoptotic effects, increasing cell viability.
• LYD activated the STING pathway, upregulated chemokines (CXCL10, CXCL9, CCL5), and reduced P70S6K/S6K proteins.
• In vivo, LYD inhibited tumor growth and increased CD8+ T cells in an NSCLC mouse model.

Conclusions:

• LYD exhibits potent anti-cancer properties against NSCLC by inducing ROS-mediated apoptosis and modulating the STING pathway and chemokines.
• LYD inhibits key cell growth proteins (P70S6K, S6K) and enhances anti-tumor immunity via CD8+ T cells.
• Lycorine demonstrates significant potential as a therapeutic agent for NSCLC treatment.