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Evaluation of LG's anticancer acti̇vi̇ty on human gastric cancer cell line HGC-27 via molecular docking and gene
Enver Ciraci1, Asiye Gok Yurttas2, Tugba Elgun3
1Department of Biochemistry, Faculty of Pharmacy, Istanbul Biruni University, Istanbul, Turkey.
Abstract:
Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies and continues to pose a significant global health burden. Repurposing clinically approved drugs is a cost-effective strategy for identifying new anticancer agents. In this study, the anticancer effects of linagliptin (LG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, were evaluated in the human gastric cancer cell line HGC-27. LG significantly reduced cell viability in a dose-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 50.29 μM, and increased apoptotic cell death as confirmed by flow cytometry. Gene expression analysis revealed significant downregulation of Smoothened (SMO) and split hand and foot malformation 1 (SHFM1) and upregulation of Sonic hedgehog (SHH), indicating modulation of Hedgehog signaling. In addition, LG treatment resulted in reduced global DNA methylation levels. Molecular docking analyses demonstrated favorable binding affinities between LG and key Hedgehog pathway proteins, supporting a potential mechanistic basis for the observed biological effects. Collectively, these findings suggest that LG exhibits antiproliferative and pro-apoptotic activity in gastric cancer cells and may represent a promising candidate for drug repurposing in gastric cancer therapy.
Insights
Linagliptin (LG), a DPP-4 inhibitor, shows anticancer effects against gastric cancer cells by reducing viability and increasing apoptosis. This drug repurposing candidate modulates Hedgehog signaling and DNA methylation.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Gastric cancer (GC) is a leading cause of cancer-related deaths globally.
- Drug repurposing offers a cost-effective approach to discovering new cancer therapies.
Purpose of the Study:
- To investigate the anticancer potential of linagliptin (LG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, in human gastric cancer cells.
- To explore the molecular mechanisms underlying LG's effects on gastric cancer.
Main Methods:
- Utilized the HGC-27 human gastric cancer cell line.
- Assessed cell viability, apoptosis (via flow cytometry), and gene expression.
- Performed molecular docking analyses to predict interactions with Hedgehog pathway proteins.
Main Results:
- LG significantly reduced gastric cancer cell viability (IC50 = 50.29 μM) and induced apoptosis.
- LG modulated Hedgehog signaling by downregulating SMO and SHFM1 and upregulating SHH.
- LG treatment decreased global DNA methylation levels.
Conclusions:
- Linagliptin demonstrates significant antiproliferative and pro-apoptotic effects in gastric cancer cells.
- LG's mechanism involves modulation of Hedgehog signaling and DNA methylation.
- LG is a potential candidate for gastric cancer drug repurposing.
