Matrine injection inhibits pancreatic cancer growth via modulating carbonic anhydrases- a network pharmacology-based study with in vitro validation
| Autor: | Chien-Shan Cheng, Ju-ying Jiao, Ping Li, Hao Chen, Zhen Chen, Pan-ling Xu |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Down-Regulation
Apoptosis Network Pharmacology chemistry.chemical_compound Alkaloids Matrine Antigens Neoplasm Pancreatic tumor Cell Line Tumor Carbonic anhydrase Pancreatic cancer Drug Discovery medicine Humans Carbonic Anhydrase IX Matrines Carbonic Anhydrases Cell Proliferation Pharmacology biology Cell Cycle Checkpoints Carbonic Anhydrase 9 Cell cycle medicine.disease Antineoplastic Agents Phytogenic Up-Regulation Pancreatic Neoplasms Gene expression profiling chemistry biology.protein Cancer research Sophora Quinolizines |
| Zdroj: | Journal of Ethnopharmacology. 287:114691 |
| ISSN: | 0378-8741 |
| Popis: | Ethnopharmacological relevance Matrine injection is a complex mixture of plant bioactive substances extracted from Sophora flavescens Aiton and Smilax glabra Roxb. Since its approval by the Chinese Food and Drug Administration (CFDA) in 1995, Matrine injection has been clinically used as a complementary and alternative treatment for various cancers; however, the underlying mechanism of pancreatic cancer treatment is yet to be elucidated. Aim of the study The present study explores the potential mechanism of matrine injection on pancreatic cancer through network pharmacology technique and in vitro experimental validation. Materials and methods Genes differentially expressed in pancreatic cancer were obtained from the Gene Expression Omnibus (GEO) database (GSE101448). The potential active components of matrine injection were selected following a literature search, and target prediction was performed by the SwissTarget Prediction database. Overlapping genes associated with survival were screened by the Gene Expression Profiling Interactive Analysis (GEPIA) database. In vitro experimental validation was performed with cell counting kit-8 (CCK-8) assay, apoptosis detection, cell cycle analysis, immunoblotting, and co-immunoprecipitation of the identified proteins. Results One thousand seven hundred genes differentially expressed among pancreatic tumor and non-tumor tissues were screened out. Sixteen active components and 226 predicted target genes were identified in matrine injection. A total of 25 potential target genes of matrine injection for the treatment of pancreatic cancer were obtained. Among them, the prognostic target genes carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) based on the GEPIA database are differently expressed in tumors compared to adjacent normal tissue. In vitro experiments, the results of CCK-8 assay, apoptosis and cell cycle analysis, immunoblotting, and co-immunoprecipitation showed that matrine injection inhibited Capan-1 and Mia paca-2 proliferation, arrested the cell cycle at the S phase, and induced apoptosis through up-regulated CA12 and down-regulated CA9. Conclusions In this study, bioinformatics and network pharmacology were applied to explore the treatment mechanism on pancreatic cancer with matrine injection. This study demonstrated that matrine injection inhibited proliferation, arrested the cell cycle, and induced apoptosis of pancreatic cancer cells. The mechanism may be related to the induction of CA12 over-expression, and CA9 reduced expression. As novel targets for pancreatic cancer treatment, Carbonic anhydrases require further study. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect