Page 63 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P23

Investigation of the molecular effects of palbociclib and celastrol combination treatment in
pancreatic cancer cells

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Setenay Simal Delioglu *, Zehra Giritlioglu *, Burcu Ayhan-Sahin , Pelin Ozfiliz-Kilbas , Ozge
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Rencuzogullari
*equal contribution
1 Istanbul Kultur University, Department of Molecular Biology and Genetics, Atakoy Campus 34156 Istanbul

Background: Pancreatic cancer is the seventh leading cause cancer-associated deaths worldwide. Drug
resistance is a major problem associated with the loss of regulation of the cell cycle in pancreatic cancer
treatment. Therefore, therapeutic approaches targeting the cell cycle gains importance in pancreatic
cancer therapy. Palbociclib is a potent CDK4/6 inhibitor that blocks Rb phosphorylation and inhibits E2F
release, leading to G1 phase arrest and suppression of tumor growth. Considering the better outcomes of
combination therapy in pancreatic cancer, a potent leptin sensitizer Celastrol is used in this study to
enhance the efficiency of palbociclib. Celastrol functions in the inhibition of the malignant progression of
cancer, maintaining the homeostasis of lipid metabolism and triggering apoptosis by regulating genes
involved in lipid synthesis and catabolism. The current study aims to elucidate the potential roles of
palbociclib and celastrol combination treatment in Panc-1, MiaPaCa-2, Capan-2, Aspc-1 pancreatic cancer
cells related to fatty acid metabolism. Results: Our results showed that individual treatment of celastrol or
palbociclib reduced cell viability and proliferation of cells in dose-dependent manner. Combinational
treatment of palbociclib and celastrol enhanced the cell viability decrease. In addition, PI3K/Akt and
epithelial-mesenchymal transition (EMT) signaling were activated by suppressing fatty acid metabolism.
Conclusion: According to our results, co-treatment of palbociclib and celastrol is a novel insight into
pancreatic cancer therapy related to elucidating the association of fatty acid and apoptotic mechanisms.

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