Imatinib-resistant kit and pdgfra wild-type gist cell lines and their construction methods and applications

Abstract

The Imatinib-resistant KIT and PDGFRA wild-type GIST cell line provided by the present invention is named GIST-FR, and is preserved in the China Center for Type Culture Collection with the preservation number CCTC NO: C2017111. At the same time, the present invention also provides the construction method of this cell line and the use of the cell line as a cell model for the investigation of the drug resistance mechanism of human gastrointestinal stromal tumors and the study of related signaling pathways. The cells were then immortalized to establish the GIST-F cell line, which was then induced with Imatinib resistance to establish the Imatinib-resistant GIST cell line GIST-FR. GIST‑FR cells have been passaged in vitro for more than 40 generations. Compared with GIST‑F cells, GIST‑FR cells grow slower, and their IC50 to Imatinib is significantly higher, with a drug resistance index of 3.52 (P<0.01). and PDGFRA were negative. The present invention successfully establishes GIST cell lines from human GIST primary tissues, and further induces its Imatinib-resistant cells, laying a foundation for the research on GIST pathogenesis and drug resistance.

Description

technical field [0001] The present invention relates to a drug-resistant cell line and its construction method and application, in particular to an Imatinib-resistant KIT and PDGFRA wild-type GIST cell line and its construction method and application. Background technique [0002] GIST (gastrointestinal stromal tumor) is the most common mesenchymal tumor in the gastrointestinal tract, accounting for about 1% to 3% of malignant tumors in the gastrointestinal tract. Studies have found that about 85% of gastrointestinal stromal tumors (GIST) have KIT (65%) or PDGFRA (20%) gene mutations. Both KIT and PDGFRA belong to the transmembrane type III tyrosine receptor family. [0003] At present, research on the pathogenesis, pathological diagnosis, and clinical treatment of gastrointestinal stromal tumors (GIST) has made great progress. Tyrosine kinase inhibitors, mainly imatinib, etc. The application of molecular targeted drugs has greatly improved the clinical efficacy of gastroi...

AI Technical Summary

Problems solved by technology

[0005] In view of the above problems, the present invention provides an Imatinib-resistant KIT and PDGFRA wild-type GIST cell line and its construction method and application, so as to overcome the current domestic imatinib-resistant KIT and PDGFRA wild-type GIST resistance. Drug-resistant cell lines make it difficult to study the pathogenesis and drug resistance mechanism of GIST, thus laying the foundation for research on GIST drug resistance and increasing the influence of the country in international medicine

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