کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8961904 | 1646524 | 2018 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hormone-dependent breast cancer: Targeting autophagy and PI3K overcomes Exemestane-acquired resistance
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کلمات کلیدی
AISDCFH2-DACCCPCFBsAVOs2′,7′-dichlorodihydrofluorescein diacetate - 2 '، 7'-dichlorodihydrofluorescein diacetateDiOC6(3) - DiOC6 (3)Acridine orange - آکاردین نارنجیAkt - آکتAromatase inhibitors - مهار کننده های آراماتازprotein kinase B - پروتئین کیناز Bcarbonyl cyanide m-chlorophenylhydrazone - کربنیل سیانید m-chlorophenylhydrazone
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered - as first-line treatment for estrogen receptor-positive (ER+) breast tumors, in postmenopausal women. Exemestane (Exe) is a powerful steroidal AI, however, despite its therapeutic success, Exe-acquired resistance may occur leading to tumor relapse. Our group previously demonstrated that autophagy acts as a pro-survival process in Exe-induced cell death of ER+ sensitive breast cancer cells. In this work, the role of autophagy and its relationship with the PI3K/AKT/mTOR pathway in Exe-acquired resistance was explored. In that way, the mechanism behind the effects of the combination of Exe with pan-PI3K, or autophagic inhibitors, was studied in a long-term estrogen deprived ER+ breast cancer cell line (LTEDaro cells). Our results indicate that Exe induces autophagy as a cytoprotective mechanism linked to acquired resistance. Moreover, it was demonstrated that by inhibiting autophagy and/or PI3K pathway it is possible to revert Exe-resistance through apoptosis promotion, disruption of cell cycle, and inhibition of cell survival pathways. This work provides new insights into the mechanisms involved in Exe-acquired resistance, pointing autophagy as an attractive therapeutic target to surpass it. Thus, it highlights new targets that together with aromatase inhibition may improve ER+ breast cancer therapy, overcoming AIs-acquired resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 183, October 2018, Pages 51-61
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 183, October 2018, Pages 51-61
نویسندگان
Cristina Amaral, Tiago Vieira Augusto, Elisiário Tavares-da-Silva, Fernanda M.F. Roleira, Georgina Correia-da-Silva, Natércia Teixeira,