The effects of PKI-402 on breast tumor models' radiosensitivity via dual inhibition of PI3K/mTOR.

Autor: Gasimli R; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Kayabasi C; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Ozmen Yelken B; Department of Medical Biology, Faculty of Medicine, Bakircay University, Izmir, Turkey., Asik A; Department of Medical Biology, Faculty of Medicine, Mugla Sitki Kocman University, Mugla, Turkey., Sogutlu F; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Celebi C; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Yilmaz Susluer S; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Kamer S; Department of Radiation Oncology, Faculty of Medicine, Ege University, Izmir, Turkey., Biray Avci C; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Haydaroglu A; Department of Radiation Oncology, Faculty of Medicine, Ege University, Izmir, Turkey., Gunduz C; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey.
Jazyk: angličtina
Zdroj: International journal of radiation biology [Int J Radiat Biol] 2023; Vol. 99 (12), pp. 1961-1970. Date of Electronic Publication: 2023 Jul 12.
DOI: 10.1080/09553002.2023.2232019
Abstrakt: Purpose: PI3K/Akt/mTOR pathway activation causes relapse and resistance after radiotherapy in breast cancer (BC). We aimed to radiosensitize BC cell lines to irradiation (IR) by PKI-402, a dual PI3K/mTOR inhibitor.
Methods: We performed cytotoxicity, clonogenicity, hanging drop, apoptosis and double-strand break detection, and phosphorylation of 16 essential proteins involved in the PI3K/mTOR pathway.
Results: Our findings showed that PKI-402 has cytotoxic efficiency in all cell lines. Clonogenic assay results showed that PKI-402 plus IR inhibited the colony formation ability of MCF-7 and breast cancer stem cell lines. Results showed that PKI-402 plus IR causes more apoptotic cell death than IR alone in the MCF-7 cells but did not cause significant changes in the MDA-MB-231. γ-H2AX levels were increased in MDA-MB-231 in PKI-402 plus IR groups, whereas we did not observe any apoptotic and γ-H2AX induction in BCSCs and MCF-10A cells in all treatment groups. Some pivotal phosphorylated proteins of the PI3K/AKT pathway decreased, several proteins increased and others did not change.
Conclusion: In conclusion, if the combined use of PKI-402 with radiation is supported by in vivo studies, it can contribute to the treatment options and the course of the disease.
Databáze: MEDLINE
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