Chaihu Shugan San Inhibits Pancreatic Cancer Invasion and Migration by Targeting the Snail/ZEB1-Mediated Epithelial–Mesenchymal Transition
Abstract
Abstract Chaihu Shugan San (CHSGS), a classic Traditional Chinese Medicine formula used to treat stress-related disorders, has been conceptually linked to tumor progression, yet its anti-cancer effects remain largely unexplored. Here we show that CHSGS significantly inhibits the migration and invasion of AsPC-1 pancreatic cancer cells in a dose-dependent manner without affecting cell viability at therapeutic concentrations (25–100 µg/mL). Network pharmacology and molecular docking predicted that CHSGS active compounds, including Quercetin and Luteolin, may target the epithelial–mesenchymal transition (EMT) machinery. Mechanistically, CHSGS reversed EMT, as reflected by upregulation of E-cadherin and downregulation of N-cadherin and Vimentin, and suppressed the master EMT transcription factors Snail and ZEB1 at both the mRNA and protein levels. Molecular docking suggested stable binding of Quercetin to Snail (− 8.5 kcal/mol) and Luteolin to ZEB1 (− 9.2 kcal/mol). Crucially, forced overexpression of Snail significantly abrogated the inhibitory effects of CHSGS on cell invasion and migration, establishing a causal role for Snail downregulation. These findings demonstrate that CHSGS suppresses pancreatic cancer cell invasion and migration by reversing EMT through the Snail/ZEB1 axis, providing a scientific rationale for CHSGS as a complementary therapy for metastatic pancreatic cancer and highlighting the Snail/ZEB1 axis as a promising anti-metastatic drug target from…
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