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Prucalopride inhibits lung cancer cell proliferation, invasion, and migration through blocking of the PI3K/AKT/mTor
1Department of Respiratory Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Abstract:
Lung cancer is the main cause of cancer incidence and mortality around the world. Prucalopride is an agonist for the 5-hydroxytryptamine 4 receptor, but it was unknown whether prucalopride could be used to treat lung cancer. To investigate the biological effects of prucalopride on proliferation, apoptosis, invasion, and migration of lung cancer cells, and its underlying molecular mechanism in the progression of lung cancer, we performed this study. The Cell Counting Kit 8 assay was used to measure the proliferation of A549/A427 lung cancer cells treated with prucalopride. Transwell assay was applied to evaluate cell invasion and migration. Cell apoptosis was detected by flow cytometry and Western blot analyses. The expression levels of related proteins in the PI3K/AKT/mTor signaling pathway were analyzed by Western blotting. Prucalopride inhibited the proliferation, invasion, and migration of A549/A427 human lung cancer cells. It also induced autophagy and apoptosis and decreased the expression of the phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTor) in these cells. This study implied an inhibitory role for prucalopride in the progression of human lung cancer.
Insights
Prucalopride, a 5-hydroxytryptamine 4 receptor agonist, was found to inhibit lung cancer progression. This study showed prucalopride reduced proliferation, invasion, and migration while inducing apoptosis in lung cancer cells.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Lung cancer remains a leading global cause of cancer incidence and mortality.
- The therapeutic potential of prucalopride, a 5-hydroxytryptamine 4 receptor agonist, in lung cancer treatment is not established.
Purpose of the Study:
- To investigate the effects of prucalopride on lung cancer cell proliferation, invasion, migration, and apoptosis.
- To elucidate the molecular mechanisms underlying prucalopride's action in lung cancer progression, focusing on the PI3K/AKT/mTor pathway.
Main Methods:
- Cell Counting Kit 8 assay for proliferation.
- Transwell assay for invasion and migration.
- Flow cytometry and Western blot for apoptosis and protein expression analysis (PI3K/AKT/mTor pathway).
Main Results:
- Prucalopride significantly inhibited proliferation, invasion, and migration of A549/A427 human lung cancer cells.
- Prucalopride treatment induced autophagy and apoptosis in lung cancer cells.
- Decreased expression of phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTor) was observed.
Conclusions:
- Prucalopride demonstrates an inhibitory role in the progression of human lung cancer.
- The findings suggest prucalopride's potential as a therapeutic agent for lung cancer, mediated partly through the PI3K/AKT/mTor signaling pathway.
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