Page 91 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

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The effect of CDK4/6 inhibition on cancer stem like-properties-induced Panc-1 and MiaPaCa-2
pancreatic cancer cells

1
2
Özge Rencüzoğulları , E. Damla Arisan
1 Istanbul Kultur University, Science and Literature Faculty, Department of Molecular Biology and Genetics, Atakoy
Campus, 34156 Istanbul/Turkey
2 Institute of Biotechnology, Gebze Technical University, Gebze 41400, Turkey

Background: Pancreatic cancer is one of the most aggressive tumor types and has remarkable resistance
mechanism to treatment due to heterogeneity of tumor cells. Another factor that causes resistance
mechanism is cancer stem cells. Leptin is an adipokine which stimulate cell proliferation, drug resistance
through an increase of Notch signaling in cancer cells. In this study, it was aimed to understand the role of
CDK4/6 inhibition in Panc-1 and MiaPaCa-2 cells, which have increased cancer stem cell-like properties due
to leptin administration.
Material and methods: Panc-1 and MiaPaCa-2 cells were exposed to leptin treatment (100 ng/ml) for 24 h.
Then, leptin-treated (leptin+) and leptin-untreated (leptin-) cells were treated by 3 μM CDK4/6 inhibitor,
palbociclib. The effect of treatments on cell viability and colony formation was observed. The response of
CDK4/6 inhibition on the stimulation of cell aggressiveness by leptin treatment was determined by
measuring CD44, CD133 and CD24 levels on flow cytometry. The effect of palbociclib on Wnt/Notch
signaling was analyzed by immunoblotting in leptin +/- Panc-1 and MiaPaCa-2 cells. Results: Leptin
treatment stimulated the cell proliferation of both Panc-1 and MiaPaCa-2 cells. Leptin-treated cells had
higher colony formation rate and the anchorage-independent growth was higher than leptin untreated
cells. Although CDK4/6 inhibition reduced the colony formation, it was obvious that leptin+ cells were more
resistant to treatment. The CD44 and CD24 levels significantly increased by leptin treatment but, inhibition
of CDK4/6 led to downregulation of both CD44 and CD24 levels in Panc-1 cells. The expression levels of
mesenchymal members, N-cadherin, β-catenin, Notch, Akt, were significantly increased in leptin+ cells.
Palbociclib treatment had remarkable effect on dowregulation of Notch levels in leptin+ Panc-1 and
MiaPaCa-2 cells. However, there was no significant effect of palbociclib on the expression levels of Akt and
β-catenin in leptin+ cells. Conclusion: CDK4/6 inhibition had significant therapeutic potential on the
regulation of cell proliferation abilities and aggressiveness of Panc-1 and MiaPaCa-2 cells with cancer stem
cell characteristics.
*This study was supported by TÜBİTAK (Project no: 119Z158) and Istanbul Kultur University Project Center.

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