Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming

Area of Science:

• Oncology
• Molecular Biology
• Metabolic Research

Background:

• Salvianolic acid B (Sal B) shows potential as a chemoprevention agent for various cancers.
• Non-small-cell lung cancer (NSCLC) metastasis remains a significant challenge in cancer treatment.

Purpose of the Study:

• To investigate the pharmacological effects of Sal B on NSCLC metastasis.
• To elucidate the underlying mechanisms, particularly focusing on metabolic reprogramming and epithelial-to-mesenchymal transition (EMT).

Main Methods:

• Utilized two NSCLC cell lines (NCI-H2030, NCI-H1650) treated with Sal B.
• Assessed cell migration and invasion using wound healing and transwell assays.
• Analyzed EMT markers (β-catenin, E-cadherin) via western blotting.
• Evaluated cellular bioenergetics including glucose uptake, lactate production, ATP levels, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR).
• Measured metabolic reprogramming markers (PKM2, LDHA, GLUT1) using western blotting and immunofluorescence.

Main Results:

• Sal B significantly weakened NSCLC cell migration and invasion.
• Sal B treatment inactivated EMT by downregulating β-catenin and upregulating E-cadherin.
• Sal B reduced cellular metabolic activity, including glucose uptake, lactate production, ATP levels, OCR, and ECAR.
• Sal B downregulated key metabolic reprogramming markers: PKM2, LDHA, and GLUT1.
• The PKM2 agonist TEPP-46 showed potential to reverse Sal B's inhibitory effects.

Conclusions:

• Sal B effectively weakens NSCLC metastasis through a PKM2-independent metabolic reprogramming pathway.
• These findings highlight Sal B's potential as a therapeutic agent for treating NSCLC.
• Further research into Sal B's mechanism could lead to novel anti-cancer strategies.