The effects of PKI-402 on breast tumor models’ radiosensitivity via dual inhibition of PI3K/mTOR
Makaleler > Tam Makale · 2023
Yazarlar: Roya Gasımlı, ÇAĞLA KAYABAŞI, BESRA ÖZMEN YELKEN, AYCAN AŞIK, FATMA SÖĞÜTLÜ, Sunde YILMAZ SÜSLÜER, Emine Serra KAMER, Çığır BİRAY AVCI, AYFER HAYDAROĞLU, Cumhur GÜNDÜZ
International Journal of Radiation Biology, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2023, cilt 99, ss 1961-1970
DOI: 10.1080/09553002.2023.2232019
Özet
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.