miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells

miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells


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نویسندگان: بهمن یوسفی , امیر ولیزاده دیزجیکان , سید مصطفی میر , انصار کریمیان

کلمات کلیدی: Keywords Colon cancer microRNA-29a Multi-drug resistance PTEN PI3K/Akt P-gp

نشریه: 55157 , 15 , 880 , 2020

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نویسنده ثبت کننده مقاله بهمن یوسفی
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز تحقیقات کاربردی دارویی
کد مقاله 73383
عنوان فارسی مقاله miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells
عنوان لاتین مقاله miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells
ناشر 8
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ خیر
عنوان نشریه (خارج از لیست فوق)
نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت

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Colon cancer is a serious malignant type of cancer in the world. Acquisition of multi-drug resistance (MDR) during chemotherapy is still a controversial challenge during cancer treatment. Accordingly, detection of safe and impressive MDR-reversing targets such as microRNAs (miRNAs/miRs) can play critical role in cancer treatment. Here, the functional effects of miR-29a in chemo-resistant colon cancer cells is scrutinized. The effect of doxorubicin (DOX) on cell proliferation after miR-29a transfection has been evaluated using MTT assay in HT29 and HT29/DOX cells. Rhodamine123 (Rh123) assay is used to identify the activity of common drug efflux through membrane transporters P-glycoprotein (P-gp). P-gp and PTEN mRNA/protein expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Flow cytometry was employed to the investigation of apoptosis. ANOVA followed by Bonferroni's and Sidak's tests were used to compare the data from different groups. Thus, it was shown that miRNA-29a overexpression considerably inhibited the HT29/DOX viability. miR-29a significantly down-regulated P-gp expression and activity in HT29/ DOX cells and declined drug resistance through elevation of intracellular DOX. Furthermore, upon miRNA-29a transfection, PTEN expression could be restored in resistant cells. These results have indicated that miR-29a target PTEN ultimately P-gp, which is downstream of PTEN, inhibit drug resistance, proliferation, and apoptosis through PI3K/Akt pathway. As a result, miR-29a overexpression is led to enhance the sensitivity of HT29/DOX cells to DOX-treatment by targeting P-gp. MiR-29a might proffer a novel promising candidate for colon cancer therapeutics during chemotherapy.

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نویسنده نفر چندم مقاله
بهمن یوسفیهشتم
امیر ولیزاده دیزجیکاندوم
سید مصطفی میرسوم
انصار کریمیانپنجم

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shi2020.pdf1399/06/182002021دانلود