تیمار ترکیبی رتینوئیک اسید تمام تذانس و گاما سکرتاز موجب مهار رشد و آپوپتوزیس در رده سلولهای سرطان معده انسان می شود

پات راد, الهام and نیاپور, علی and فراستی, فریس and امانی, مجتبی (1397) تیمار ترکیبی رتینوئیک اسید تمام تذانس و گاما سکرتاز موجب مهار رشد و آپوپتوزیس در رده سلولهای سرطان معده انسان می شود. Cytotechnology ــ 70 (2). pp. 865-877. شاپا 0920-9069

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Official URL: https://link.springer.com/article/10.1007/s10616-0...


Combination treatment of all-trans retinoic acid (ATRA) and γ-secretase inhibitor (DAPT) cause growth inhibition and apoptosis induction in the human gastric cancer cell line

English Abstract

Current medication for gastric cancer patients has a low success rate with resistance and side effects. According to recent studies, γ-secretase inhibitors is used as therapeutic drugs in cancer. Moreover, all-trans retinoic acid (ATRA) is a natural compound proposed for the treatment/chemo-prevention of cancers. The aim of this study was to explore the effects of ATRA in combination with N-N-(3,5-difluorophenacetyl-l-alanyl)-S-phenylglycine t-butyl ester (DAPT) as $\gamma$-secretase inhibitor on viability and apoptosis of the AGS and MKN-45 derived from human gastric cancer. AGS and MKN-45 gastric cancer cell lines were treated with different concentrations of ATRA or DAPT alone or ATRA plus DAPT. The viability, death detection and apoptosis of cells was examined by MTT assay and Ethidium bromide/acridine orange staining. The distribution of cells in different phases of cell cycle was also evaluated through flow cytometry analyses. In addition, caspase 3/7 activity and the expression of caspase-3 and bcl-2 were examined. DAPT and ATRA alone decreased gastric cancer cells viability in a concentration dependent manner. The combination of DAPT and ATRA exhibited significant synergistic inhibitory effects. The greater percentage of cells were accumulated in G0/G1 phase of cell cycle in combination treatment. The combination of DAPT and ATRA effectively increased the proportion of apoptotic cells and the level of caspase 3/7 activities compared to single treatment. Moreover, augmented caspase-3 up-regulation and bcl-2 down-regulation were found following combined application of DAPT and ATRA. The combination of DAPT and ATRA led to more reduction in viability and apoptosis in respect to DAPT or ATRA alone in the investigated cell lines.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :الهام پات راد
نویسنده مسئول :علی نیاپور
نویسنده :فریس فراستی
نویسنده مسئول :مجتبی امانی
Additional Information:Impact Factor (2016) 1.857 Indexed in: ISI, Scopus, EMBASE, Google Scholar, CAB International, Academic OneFile, AGRICOLA, Biological Abstracts, BIOSIS, CAB Abstracts, CNKI, Current Abstracts, Current Contents/ Agriculture, Biology & Environmental Sciences, EBSCO Biotechnology Collection: India , EBSCO Science & Technology Collection, EBSCO TOC Premier, Elsevier Biobase, EMBiology, Gale, Global Health, International Bibliography of Book Reviews (IBR), International Bibliography of Periodical Literature (IBZ), OCLC, ProQuest Biological Science Database, ProQuest Natural Science Collection, ProQuest SciTech Premium Collection
کلیدواژه ها (انگلیسی):DAPT, ATRA Gastric, cancer Caspase 3/7, bcl-2, Combination therapy
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
QU Biochemistry
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of Biochemistry
ID Code:9818
Deposited By: Dr Mojtaba Amani
Deposited On:28 Nov 1396 11:04
Last Modified:13 Jun 1397 09:33

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