Effect of Wenxia Changfu Formula Combined With Cisplatin Reversing Non-Small Cell Lung Cancer Cell Adhesion-Mediated Drug Resistance

Abstract

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 b1 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 b1 overexpression. In vitro, the cell viability, migration and adhesion were measured though MTT Assay, Wound Healing Assay and Cell Adhesion Assay, the Integrin b1 expression of the A549 cells was assessed through immunocytochemistry; in vitro, the transplanted tumor morphology and the colocalization of Integrin b1 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 b1 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 b1 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 b1 signaling pathway.

Transcriptome and Metabolome Analysis Revealed the Freezing Resistance Mechanism in 60-Year-Old Overwintering Camellia sinensis

“…Next, the data were extracted using Compound Discover V3.1 (CD) software, including noise filtering, retention time alignment, mass spectrometry peak extraction, compound mapping between samples, compound identification, gap filling, and background subtracting. Meanwhile, compounds were identified using the mzCloud and ChemSpider database [40][41][42]. Finally, based on the quality control (QC) sample, it was filtered, and data standardization and normalization were achieved by the Constant SUM and Auto Scaling algorithm [43,44].…”

Identifying PIF1 as a Potential Target of Wenxia Changfu Formula in Promoting Lung Cancer Cell Apoptosis: Bioinformatics Analysis and Biological Evidence

“…The UHPLC/MS analysis was performed according to the procedure we had reported elsewhere [ 18 ]. In brief, UHPLC analysis was performed on an UltiMate 3000 RS system (Thermo Fisher Scientific, San Diego, CA).…”

“…Previous studies have demonstrated that WCF has a significant antitumor effect as it inhibits the A549 cell line proliferation and induces lung cancer cell apoptosis [ 16 , 17 ]. Furthermore, WCF effectively enhances chemotherapeutic efficacy and reverses multidrug resistance mediated by cell adhesion in lung cancer cells, the mechanism of which may be related to the integrin β 1 signaling pathway [ 18 , 19 ]. Herb formula of TCM is characterized by multitarget, multibiological process and multipathway [ 20 ].…”

Traditional Herbal Medicine: A Potential Therapeutic Approach for Adjuvant Treatment of Non-small Cell Lung Cancer in the Future

“… 110 Previous studies revealed that WXC prescriptions with cisplatin may effectively suppress tumors by block the cell cycle and induce apoptosis. 111 , 112 …”