Palbociclib induces cell senescence and apoptosis of gastric cancer cells by inhibiting the Notch pathway

Bi,Hengtai; Shang,Juan; Zou,Xiao; Xu,Jing; Han,Yumei

doi:10.3892/ol.2021.12864

Palbociclib induces cell senescence and apoptosis of gastric cancer cells by inhibiting the Notch pathway

Authors:
- Hengtai Bi
- Juan Shang
- Xiao Zou
- Jing Xu
- Yumei Han
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Affiliations: Department of Pharmacy, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Pharmacy, The People's Hospital of Bin Zhou, Bin Zhou, Shandong 256600, P.R. China, Department of Oncology, The First People's Hospital of Tai'an, Tai'an, Shandong 271000, P.R. China, Department of Neurology, The First People's Hospital of Tai'an, Tai'an, Shandong 271000, P.R. China, Department of General Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: June 10, 2021 https://doi.org/10.3892/ol.2021.12864
Article Number: 603
Copyright: © Bi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Palbociclib (PD0332991), a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has been reported to exert anticancer activity in some cancers, including gastric cancer (GC). However, the role of palbociclib in GC remains largely unknown. The present study aimed to investigate the effects of palbociclib on the progression of GC and the potential mechanisms underlying its effects. The colony formation, proliferation, senescence, as well as apoptosis and cell cycle progression of AGS and HGC‑27 cells following treatment with palbociclib were analyzed using colony formation assays, MTT assays, senescence‑associated β‑galactosidase (SA‑β‑gal) staining and flow cytometry, respectively. The protein expression levels of Bax, Caspase‑3, Bcl‑2, p16, p21, p53, Notch1, Notch2 and hairy and enhancer of split 1 (Hes1) were measured in AGS and HGC‑27 cells using western blotting. Moreover, the mRNA expression levels of Notch1, Notch2 and Hes1 in AGS and HGC‑27 cells were determined by reverse transcription‑quantitative PCR. In the present study, palbociclib significantly inhibited cell proliferation and induced cell senescence, cell cycle arrest and apoptosis in both cell lines in a dose‑dependent manner. Additionally, palbociclib significantly increased the expression levels of Bax, Caspase‑3, p16, p21 and p53, whilst decreasing the expression of Bcl‑2, Notch1, Notch2 and Hes1 in AGS and HGC‑27 cells. Furthermore, the Notch pathway activator Jagged‑1/FC reversed the effects of palbociclib on cell proliferation, apoptosis, senescence and cell cycle progression. These findings demonstrated that palbociclib could inhibit proliferation and induce senescence, cell cycle arrest and apoptosis in GC cells by inhibiting the Notch pathway.

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