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Updated: Jun 27, 2025
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Senolysis of gemcitabine-induced senescent human pancreatic cancer cells
Mohammad Mahbubul Hoque1, Yuichi Iida1, Hitoshi Kotani1
1Department of Immunology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
Introduction:
Gemcitabine (GEM) is often used to treat pancreatic cancer. Many anti-cancer drugs induce cancer cell death, but some cells survive after cell cycle arrest. Such a response to DNA damage is termed cellular senescence. Certain drugs, including the Bcl-2-family inhibitor ABT-263, kill senescent cells; this is termed senolysis. In this study, we examined the therapeutic benefits of ABT-263 in GEM-induced senescence of human pancreatic cancer cells.
Methods And Results:
Of four pancreatic cancer cell lines (PANC-1, AsPC-1, CFPAC-1, and PANC10.05), GEM induced senescent features in PANC-1 and AsPC-1 cells, including increases in the cell sizes and expression levels of mRNAs encoding interleukin (IL)-6/IL-8 and induction of β-galactosidase. Successive treatment with GEM and ABT-263 triggered apoptosis in PANC-1 and AsPC-1 cells and suppressed colony formation significantly. Senolysis of GEM-induced senescent pancreatic cancer cells by ABT-263 was triggered by a Bcl-xL inhibitor, but not by a Bcl-2 inhibitor, suggesting a central role for Bcl-xL in senolysis. In a xenograft mouse model, combined treatment with GEM and ABT-737 (an ABT-263 analog exhibiting the same specificity) suppressed in vivo growth of AsPC-1 significantly.
Conclusion:
Together, our results indicate that sequential treatment with GEM and senolytic drugs effectively kill human pancreatic cancer cells.
