Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer

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dc.contributor.authorOzates, Neslihan Pinar
dc.contributor.authorSogutlu, Fatma
dc.contributor.authorLerminoglu, Ferzan
dc.contributor.authorDemir, Busra
dc.contributor.authorGunduz, Cumhur
dc.contributor.authorShademan, Behrouz
dc.contributor.authorAvci, Cigir Biray
dc.date.accessioned2021-05-03T20:33:30Z
dc.date.available2021-05-03T20:33:30Z
dc.date.issued2021
dc.departmentEge Üniversitesien_US
dc.description.abstractBreast cancer is the most common cancer in women and the leading cause of cancer mortality in women over 40 it's the year. The existence of the PI3K/AKT/mTOR pathway aberrations in more than 70% of breast cancer has caused to become a therapeutic target. AZD3463 is an anti-cancer agent used as a potential inhibitor of ALK/IGF1R. It also induces apoptosis and autophagy of the PI3K/AKT/mTOR pathway in cancer cells. Although the mTOR signaling might be inhibited by rapamycin treatment, signals transmitted from the upstream pathway supports cell survival and proliferation. The WST-1 assay test was performed to evaluate the anti-proliferative effects of rapamycin and AZD3463. Besides, the effects of them on apoptosis, autophagy, cytostatic, and metabolism in MCF7 breast cancer cells were investigated. Also, changes in the expression of apoptotic regulatory genes, cell cycle, and metabolism in the PI3K/AKT/mTOR Pathway were determined by Quantitative RT-PCR. The results showed that rapamycin and AZD3463 treatments significantly reduced survival in MCF7 cells. Also, apoptosis, autophagy, and cell population in the G0/G1 stage in the MCF7 cell category in the treatment group showed an increase compared to the control group. The combination of rapamycin and AZD3463 (AZD-RAPA) was determined as an additive according to isobologram analysis. in the combination of rapamycin with AZD3463, the expression of CDKN1B, PTEN, FOXO3, and APC genes increases, and the expression of PRKCB and PIK3CG genes decreases. Our results showed that the use of AZD-RAPA reduced the resistance of cancer cells to treatment and it leads cancer cells to apoptosis.en_US
dc.identifier.doi10.1016/j.lfs.2020.118643en_US
dc.identifier.issn0024-3205
dc.identifier.issn1879-0631
dc.identifier.pmid33141044en_US
dc.identifier.urihttps://doi.org/10.1016/j.lfs.2020.118643
dc.identifier.urihttps://hdl.handle.net/11454/70049
dc.identifier.volume264en_US
dc.identifier.wosWOS:000600546400042en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.ispartofLife Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAutophagyen_US
dc.subjectBreast canceren_US
dc.subjectDrug resistanceen_US
dc.subjectmTOR signaling pathwaysen_US
dc.subjectRapamycinen_US
dc.titleEffects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast canceren_US
dc.typeArticleen_US

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