Salvianolic Acid B Suppresses Epithelial-Mesenchymal Transition-Associated Phenotypes in Cervical Cancer Cells via GPIb Alpha/LYN/TWIST1 Signaling.

Abstract

Cervical cancer remains a major gynecological malignancy, and the epithelial-mesenchymal transition is associated with tumor progression. Salvianolic acid B, a water-soluble polyphenolic compound derived from Salvia miltiorrhiza, has antitumor potential in several cancers, but its role in cervical cancer-related epithelial-mesenchymal transition signaling remains incompletely understood. HeLa and SiHa cervical cancer cells were treated with salvianolic acid B, alone or combined with modulation of platelet glycoprotein Ib alpha or Src-family kinase signaling. Cell viability, wound closure, and proliferative activity were assessed by Cell Counting Kit-8, wound healing, and 5-ethynyl-2'-deoxyuridine incorporation assays. Epithelial-mesenchymal transition markers and LYN/TWIST1 signaling components were analyzed by immunofluorescence and Western blotting. Platelet glycoprotein Ib alpha was modulated by plasmid-mediated overexpression or small interfering RNA-mediated knockdown. Salvianolic acid B reduced cervical cancer cell viability, wound closure, and 5-ethynyl-2'-deoxyuridine-positive staining, decreased N-cadherin and Vimentin, and increased E-cadherin expression. It also downregulated platelet glycoprotein Ib alpha, reduced LYN phosphorylation, and TWIST1 expression. Platelet glycoprotein Ib alpha overexpression partially attenuated these changes; knockdown enhanced them. PP2, a non-selective Src-family kinase inhibitor, also reduced TWIST1 expression and 5-ethynyl-2'-deoxyuridine-positive staining. Salvianolic acid B suppresses cervical cancer cell viability, wound closure, proliferative activity, and molecular changes associated with the epithelial-mesenchymal transition, in part through modulation of a proposed platelet glycoprotein Ib alpha/LYN/TWIST1 signaling axis. Because wound closure was measured under conditions in which viability and proliferation were also reduced, wound healing data should not be interpreted as independent evidence of impaired migration. Further preclinical validation is warranted.