Non-small cell lung cancer (NSCLC), the major form of primary
lung cancer, is a common cause of
cancer-related death worldwide. Cell adhesion-mediated drug resistance (CAM-DR), a form of
chemotherapy resistance, has been reported to confer resistance to various chemotherapeutic agents.
Integrin β1 signaling plays an important role in CAM-DR and has been proposed as a potential target for NSCLC.
Wenxia Changfu Formula (WCF) is a Traditional Chinese Compound Prescription for the intervention treatment of NSCLC combined with
cisplatin (DDP). This study aims to investigate the effect and mechanism of WCF combined with DDP in reversing CAM-DR. Firstly, the chemical profile of WCF was characterized by UPLC/Q-TOF-MS analysis. A total of 237 compounds with mzCloud Best Match of greater than 70 were identified by using the online database mzCloud. Secondly, we established A549 three-dimensional(3D) cells cultured in vitro and nude mice xenografts models of the A549 cell line with
Integrin β1 overexpression. In vitro, the cell viability, migration and adhesion were measured though MTT Assay, Wound Healing Assay and Cell Adhesion Assay, the
Integrin β1 expression of the A549 cells was assessed through immunocytochemistry; in vitro, the transplanted
tumor morphology and the colocalization of
Integrin β1 and its
ligands were tested by HE staining and immunofluorescence. As a result, we found that the combination effectively reduced cell viability, suppressed migration and adhesion, and downregulated the
protein level of
Integrin β1 in three-dimensional cultured A549 cells. And the combination of WCF with DDP significantly inhibited
tumor growth, increased organelle vacuolations and decreased colocalization of
Integrin β1 and its
ligands including
fibulin-2 and
laminin. Taken together, our results confirm that the combination of WCF with DDP could reverse the
lung cancer CAM-DR through the
Integrin β1 signaling pathway.