پورامامعلی, فرهاد ، جدی, فرهاد ، صمدی, ناصر (1399) در سلولهای سرطان معده، محور Nrf2-ME1 با مقاومت به 5- فلوئورویوراسیل همبستگی دارد. Process Biochemistry ــ 1 Febr (01.033). ص.ص.1-5. شاپا 1359-5113 (در حال چاپ )
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آدرس اینترنتی رسمی : https://www.sciencedirect.com/science/article/abs/...
عنوان انگليسی
Nrf2-ME-1 axis is associated with 5-FU resistance in gastric cancer cell line
خلاصه انگلیسی
The aim of this study was to investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and key downstream targeting molecule, malic enzyme-1 (ME-1), in the induction of 5-fluorouracil (5-FU) resistance. Resistant MKN-45 (MKN-45/DR) cell line was generated by employing IC50 concentration of the agent followed by a resting cycles. Cell viability and apoptosis were evaluated by MTT assay, DAPI staining and flow cytometry. mRNA expression levels of Nrf2 and ME-1 were measured by qRT-PCR technique. Morphology analysis and combination index calculation were assessed by ImagJ and compuSyn softwares, respectively. The value for IC50 in 5-FU resistant cells increased from 8.81 ± 0.209–142.4 ± 0.060 μM with a considerable morphological changes from round to elongated shape (p = 0.016). Nrf2 and ME-1 expression levels were decreased in resistant cells with a marked increase in MDR1 mRNA level compared to sensitive cells. Combination of Nrf2 inhibitors, luteolin and brusatol had synergistic effects on 5-FU induced cytotoxicity. Moreover, combined incubation of MKN-45/DR cells with these inhibitors, exponentially increased Nrf2 and ME-1 mRNA levels (p < 0.001). Our findings suggest that the combined application of Nrf2 inhibitors, can be considered as a novel strategy to overcome 5-FU resistance in GC patients.
نوع سند : | مقاله |
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زبان سند : | انگلیسی |
نویسنده اول : | فرهاد پورامامعلی |
نویسنده : | فرهاد جدی |
نویسنده مسئول : | ناصر صمدی |
ضریب تاثیر و نمایه مجلات: | IF: 2.883 Indexed in: ISI, Scopus |
کلیدواژه ها (انگلیسی): | Gastric cancer , 5-FU , Nrf2 , ME-1 , Drug resistance |
موضوعات : | QU بیوشیمی WI سیستم گوارشی |
بخش های دانشگاهی : | دانشكده پزشكي > گروه علوم پایه > بخش علوم تشريح |
کد شناسایی : | 13034 |
ارائه شده توسط : | دکتر فرهاد جدی |
ارائه شده در تاریخ : | 23 تیر 1399 08:29 |
آخرین تغییر : | 23 تیر 1399 08:29 |
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