The Senescence Program is Reduced in Proteasome Inhibitor Bortezomib-Resistant PC3 Prostate Cancer Cell Line

Year 2023, Volume: 82 Issue: 1, 49 - 58, 26.06.2023

Ertan Kanbur , Semih Şeker , Ferah Budak , Azmi Yerlikaya

Abstract

Objective: Senescence may act as an antitumor mechanism by preventing the proliferation of cancer cells. Here we investigated the hypothesis that PC3 prostate cancer cells resistant to bortezomib respond differently to proteasomal inhibition with respect to induction of the senescence program as compared to the parental cells.
Materials and Methods: The degree of senescence was measured by 𝛽-galactosidase activity and the level of senescenceassociated p16 INK4a by Western blotting after treatment of cells with varying concentrations of bortezomib. In addition, the senescence-associated secretory phenotype was analyzed by Human Cytokine Antibody Array.
Results: It is reported that the basal level of senescence was lower in resistant cells compared to non-resistant cells. It was found that the basal level of the senescence marker p16 INK4a was lower in bortezomib-resistant cells than in parent non-resistant cells. Moreover, p16 INK4a was significantly reduced in both cells under conditions of 100 nM bortezomib treatment, a finding suggesting that the reduced senescence after proteasomal inhibition was likely due to the reduced levels of p16 INK4a. Finally, it is reported here for the first time that basal levels of the proteins NAP2, FGF-6, MIP-3𝛼, and PARC are significantly increased in the resistant cells compared to the parental cells.
Conclusion: Overall, the results suggest that inhibition of senescence may play an important function in the development of resistance to bortezomib.

Keywords

Bortezomib, cancer, prostate, proteasome, p16 INK4a, senescence

Supporting Institution

The Scientific Research Projects Coordination Unit of Kutahya Health Sciences University

Project Number

TSA-2021-56

Thanks

We would like to acknowledge the financial support by the Scientific Research Projects Coordination Unit of Kutahya Health Sciences University with Grant No. TSA-2021-56.

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