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- Title
Apatinib combined with Keytruda treatment induces apoptosis of gastric carcinoma cells through CES4/miR‐616‐5p/DUSP2 axis.
- Authors
Zhang, Fengli; Yin, Yanfen; Xu, Wenwen; Zhou, Zhou; Sun, Xin; Li, Ping
- Abstract
Gastric carcinoma (GC) is a highly malignant and heterogeneous tumour. Long non‐coding RNA CES4 is down‐regulated in GC. However, whether CES4 can participate in GC remains unclear; we have carried out research on this topic. GC cells (HGC‐27 and MKN‐7) were treated with anti‐tumour drugs: apatinib combined with Keytruda. Cell viability and apoptosis were detected by CCK‐8 assay and flow cytometry. Gene and protein expression were examined by quantitative real‐time PCR and western blot. Luciferase reporter assay was performed to verify the relationship among CES4, miR‐616‐5p and dual‐specificity phosphatase‐2 (DUSP2). CES4 was highly expressed in the apatinib combined with Keytruda‐treated HGC‐27 and MKN‐7 cells. Apatinib combined with Keytruda treatment repressed cell viability and promoted apoptosis of HGC‐27 and MKN‐7 cells, which was abrogated by CES4 knockdown. Furthermore, CES4 promoted DUSP2 expression by sponging miR‐616‐5p in HGC‐27 and MKN‐7 cells. CES4 knockdown promoted cell viability and inhibited apoptosis of drug‐treated HGC‐27 and MKN‐7 cells by regulating miR‐616‐5p/DUSP2 axis. In conclusion, these data demonstrate that apatinib combined with Keytruda treatment induces apoptosis of GC cells through CES4/miR‐616‐5p/DUSP2 axis. Thus, this work provides the experimental basis for the combination of apatinib and Keytruda as a treatment for GC.
- Subjects
STOMACH cancer; PEMBROLIZUMAB; LINCRNA; CELL survival; PROTEIN expression; APATINIB
- Publication
Basic & Clinical Pharmacology & Toxicology, 2021, Vol 129, Issue 5, p345
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/bcpt.13641