Triptolide Triggers Protective Autophagy via ROS Induction in NSCLC: Therapeutic Synergy with Autophagy Inhibition

Area of Science:

• Molecular Biology
• Cancer Research
• Pharmacology

Background:

• Triptolide (TPL), derived from Tripterygium wilfordii, possesses anti-inflammatory, immunomodulatory, and antitumor properties.
• Reactive oxygen species (ROS) influence cell fate, and TPL is known to induce ROS accumulation, but its role in non-small cell lung cancer (NSCLC) is not fully understood.
• Autophagy, a cellular process, can promote survival under stress but also contribute to cell death.

Purpose of the Study:

• To investigate the role of ROS-mediated autophagy in TPL-induced cytotoxicity in NSCLC.
• To evaluate the therapeutic potential of combining TPL with autophagy inhibition for NSCLC treatment.

Main Methods:

• In vitro experiments assessed TPL's effects on NSCLC cell proliferation, migration, and ROS production.
• Western blotting and fluorescence microscopy analyzed autophagy- and apoptosis-related molecular changes.
• An H1299 xenograft mouse model was used to evaluate in vivo antitumor efficacy and combination effects.

Main Results:

• TPL induced NSCLC cell death primarily by increasing ROS levels.
• ROS accumulation activated a protective autophagic response.
• Combination therapy with TPL and the autophagy inhibitor chloroquine significantly suppressed tumor growth more than either agent alone.

Conclusions:

• Autophagy functions as a resistance mechanism against TPL-induced cytotoxicity in NSCLC.
• Pharmacological inhibition of autophagy potentiates TPL's antitumor activity.
• Combining TPL with autophagy inhibitors offers a promising therapeutic strategy for NSCLC.