title: The role of captopril and losartan in prevention and regression of tamoxifen-induced resistance of breast cancer cell line MCF-7: an in vitro study.
abstract: Innate and acquired tamoxifen (TAM) resistance in estrogen receptor positive (ER+) breast cancer is an important problem in adjuvant endocrine therapy. The underlying mechanisms of TAM resistance is yet unknown. In the present study, we evaluated the role of renin-angiotensin system (RAS) in the acquisition of TAM resistance in human breast cancer cell line MCF-7, and the potential role of captopril and captopril+losartan combination in the prevention and reversion of the TAM resistant phenotype. MCF-7 cells were continuously exposed to 1 μmol/L TAM to develop TAM resistant cells (TAM-R). MTT cell viability assay was used to determine the growth response of MCF-7 and TAM-R cells, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess angiotensin I converting enzyme (ACE), angiotensin II receptor type-1 and type-2 (AGTR1 and AGTR2) mRNA expressions. Preventive and therapeutic effects of RAS blockers - captopril and losartan - were examined on MCF-7 and TAM-R cells. Based on qRT-PCR, TAM-R cells compared to MCF-7 cells, had a mean ± SD fold increase of 319.1 ± 204.1 (P = 0.002) in production of ACE mRNA level, 2211.8 ± 777.9 (P = 0.002) in AGTR1 mRNA level, and 265.9 ± 143.9 (P = 0.037) in production of AGTR2 mRNA level. The combination of either captopril or captopril+losartan with TAM led to the prevention and even reversion of TAM resistant phenotype.
authors: Department of pharmacotherapy, School of pharmacy, Shiraz university of medical sciences, PO Box 1583, 71345 Shiraz, Iran. Electronic address: namazisoha@yahoo.com.
authors: Soha
authors: S
authors: Namazi
authors: Department of pharmacotherapy, School of pharmacy, Shiraz university of medical sciences, PO Box 1583, 71345 Shiraz, Iran. Electronic address: javadrostami67@yahoo.com.
authors: Javad
authors: J
authors: Rostami-Yalmeh
authors: Department of pharmacotherapy, School of pharmacy, Shiraz university of medical sciences, PO Box 1583, 71345 Shiraz, Iran. Electronic address: ebrahimsahebi@yahoo.com.
authors: Ebrahim
authors: E
authors: Sahebi
authors: Shiraz institute for cancer research, Shiraz university of medical sciences, PO Box 1798, 71345 Shiraz, Iran. Electronic address: jaberim@sums.ac.ir.
authors: Mansooreh
authors: M
authors: Jaberipour
authors: Shiraz institute for cancer research, Shiraz university of medical sciences, PO Box 1798, 71345 Shiraz, Iran. Electronic address: razmkhahm@sums.ac.ir.
authors: Mahboobeh
authors: M
authors: Razmkhah
authors: Shiraz institute for cancer research, Shiraz university of medical sciences, PO Box 1798, 71345 Shiraz, Iran. Electronic address: hosseiniahmad@yahoo.com.
authors: Ahmad
authors: A
authors: Hosseini
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D012084:Renin-Angiotensin System / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D012333:RNA, Messenger; D013629:Tamoxifen; D002216:Captopril; D019808:Losartan
keywords: Breast cancer; Captopril; Losartan; Renin–angiotensin system; Tamoxifen resistance