هدف قرار دادن ناقل های ABC و غلبه بر مقاومت دارویی سلولهای سرطانی
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هدف قرار دادن ناقل های ABC و غلبه بر مقاومت دارویی سلولهای سرطانی

عنوان فارسی مقاله: IRE1α با هدف قرار دادن ناقل های ABC غلبه میکند بر مقاومت دارویی سلولهای سرطان کولون
عنوان انگلیسی مقاله: IRE1α-targeting downregulates ABC transporters and overcomes drug resistance of colon cancer cells
مجله/کنفرانس: اسناد سرطان - Cancer Letters
رشته های تحصیلی مرتبط: پزشکی، داروسازی
گرایش های تحصیلی مرتبط: ایمنی شناسی، داروشناسی، گوارش و کبد، خون و انکولوژی، پزشکی مولکولی
کلمات کلیدی فارسی: سرطان کولون، IRE1α، ناقل ABC، مقاومت دارویی
کلمات کلیدی انگلیسی: Colon cancer، IRE1α، ABC transporter، Drug resistance
نوع نگارش مقاله: مقاله پژوهشی (Research Article)
نمایه: Scopus - Master Journals List - JCR - MedLine
شناسه دیجیتال (DOI): https://doi.org/10.1016/j.canlet.2020.02.007
دانشگاه: Shanghai Institute of Nutrition and Health, Shanghai Institutes of Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
ناشر: الزویر - Elsevier
نوع ارائه مقاله: ژورنال
نوع مقاله: ISI
سال انتشار مقاله: 2020
ایمپکت فاکتور: 6/563 در سال 2019
شاخص H_index: 161 در سال 2020
شاخص SJR: 2/240 در سال 2019
شناسه ISSN: 0304-3835
شاخص Quartile (چارک): Q1 در سال 2019
فرمت مقاله انگلیسی: PDF
تعداد صفحات مقاله انگلیسی: 34
وضعیت ترجمه: ترجمه نشده است
قیمت مقاله انگلیسی: رایگان
آیا این مقاله بیس است: خیر
آیا این مقاله مدل مفهومی دارد: ندارد
آیا این مقاله پرسشنامه دارد: ندارد
آیا این مقاله متغیر دارد: ندارد
کد محصول: E14785
رفرنس: دارای رفرنس در داخل متن و انتهای مقاله
فهرست انگلیسی مطالب

Abstract


1- Introduction


2- Materials and methods


3- Results


4- Discussion


References

نمونه متن انگلیسی مقاله

Abstract


Drug resistance is a big problem in cancer treatment and one of the most prominent mechanisms underlain is overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2. Inhibition of ABC transporters is an important approach to overcome drug resistance. The inositol-requiring enzyme 1α (IRE1α), an arm of unfolded protein response (UPR), splices XBP1 mRNA to generate an active transcription factor XBP1s. UPR is implicated in drug resistance. However, the underlying mechanism is unclear. We found that the anticancer drugs such as 5-fluorouracil (5-FU) activated the IRE1α-XBP1 pathway to induce the expression of ABCB1, ABCC1 and ABCG2 in colon cancer cells. Inhibition of IRE1α RNase activity with small molecule 4μ8c suppressed the drug-induced expression of these ABC transporters and sensitized 5-FU-resistant colon cancer cells to drug treatment. In vivo xenograft assay indicates that administration of 4μ8C substantially enhanced the efficacy of 5-FU chemotherapy on 5-FU-resistant colon cancer cells. These results suggest that IRE1α-targeting might be a strategy to cope with drug resistance of colon cancer.


Introduction


Cancers have the ability to develop resistance to chemotherapy, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. Multidrug resistance is a phenomenon by which, after exposure to a chemotherapeutic agent, cancer cells develop resistance, and simultaneous cross-resistance, to a wide range of functionally and structurally unrelated chemotherapeutic drugs (1, 2). Intrinsic or acquired multidrug resistance is one of the main reasons for chemotherapy failure, leading to the recurrence of malignant tumors and ultimately, patient relapse or death (3). A variety of mechanisms have been attributed to multidrug resistance, such as enhanced drug efflux, increased DNA damage repair, reduced apoptosis, elevated autophagy, and/or altered drug metabolism (4-6). Previous studies have confirmed that multidrug resistance both in cancer cell lines and human tumor tissues is most often associated with the overexpression of the ATP-binding cassette (ABC) transporters (4, 7, 8). These ABC transporters are efflux pumps that transport various structurally unrelated and potentially dangerous substances out of the cells. They hydrolyze ATP for energy and actively pump drug components out of cells, leading to drug resistance. In these transporters, ABCB1 (also known as MDR1 or P-gp), ABCC1 (MRP1) and ABCG2 (BCRP1) play an important role in drug resistance in vivo (4, 7). Developing inhibitors of ABC transporters is an important approach to overcoming drug resistance. Extensive efforts have been made to develop inhibitors targeting ABC transporters, particularly ABCB1. However, no such agents have been developed successfully as was initially hoped.

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هدف قرار دادن ناقل های ABC و غلبه بر مقاومت دارویی سلولهای سرطانی
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