چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده ثبت کننده مقاله | امیر ولیزاده دیزجیکان |
| مرحله جاری مقاله | تایید نهایی |
| دانشکده/مرکز مربوطه | کمیته تحقیقات دانشجویی |
| کد مقاله | 86291 |
| عنوان فارسی مقاله | The role of linarin in increasing the sensitivity to 5-fluorouracil in colorectal cancer cells by targeting the PI3K/AKT/FOXO3a pathway |
| عنوان لاتین مقاله | The role of linarin in increasing the sensitivity to 5-fluorouracil in colorectal cancer cells by targeting the PI3K/AKT/FOXO3a pathway |
| نوع ارائه | سخنرانی |
| عنوان کنگره / همایش | هجدهمین کنگره ملی و نهمین کنگره بین المللی بیوشیمی و بیولوژی مولکولی |
| نوع کنگره / همایش | بین المللی |
| کشور محل برگزاری کنگره/ همایش | Iran (Islamic Republic) |
| شهر محل برگزاری کنگره/ همایش | تهران |
| سال انتشار/ ارائه شمسی | 1403 |
| سال انتشار/ارائه میلادی | 2024 |
| تاریخ شمسی شروع و خاتمه کنگره/همایش | 1403/08/02 الی 1403/08/04 |
| آدرس لینک مقاله/ همایش در شبکه اینترنت | https://abi.tums.ac.ir/index.php/abi/issue/view/9 |
| آدرس علمی (Affiliation) نویسنده متقاضی | Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran |
| نویسنده | نفر چندم مقاله |
|---|---|
| امیر ولیزاده دیزجیکان | اول |
| بهمن یوسفی | دوم |
| عنوان | متن |
|---|---|
| کلمات کلیدی | Colorectal cancer, linarin, 5-fluorouracil, PI3K/AKT/FOXO3a pathway, Drug resistance |
| خلاصه مقاله | Background Colorectal cancer (CRC) remains a formidable health burden challenge worldwide, with drug resistance complicating treatment. Combination therapies with natural compounds that can potentiate the anti-cancer effects of chemotherapeutics agents and overcome resistance mechanisms represent a promising therapeutic strategy. This study explores the potential of linarin, a plant-derived flavonoid, to enhance 5-fluorouracil (5-Fu) efficacy in CRC cells. Methods Using SW480 cells, we investigated the combined effects of linarin and 5-Fu on cell viability, apoptosis, and migration. Molecular mechanisms were probed via qPCR and Western blotting, focusing on the PI3K/AKT/FOXO3a pathway. We established 5-Fu-resistant cells to evaluate resistance reversal. In vivo studies utilized a DMH-induced rat model. Pharmacokinetic interactions were assessed in rats. Results Our findings revealed synergistic cytotoxicity between linarin and 5-Fu, with enhanced apoptosis and reduced migration. Mechanistically, the combination modulated the PI3K/AKT/FOXO3a pathway more effectively than either agent alone. Both linarin and 5-Fu independently inhibit the phosphorylation of Akt, leading to the activation of the pro-apoptotic transcription factor FOXO3a and the subsequent upregulation of Bax while downregulating Bcl-2. Linarin partially reversed 5-Fu resistance in SW480-5FuR cells. In vivo, the combination significantly reduced tumor burden without apparent toxicity. Pharmacokinetic studies showed mutual influences, potentially contributing to enhanced efficacy. Conclusion These findings highlight linarin's potential as an adjuvant to 5-Fu, offering a novel approach to improving CRC treatment outcomes. The unique synergistic mechanism via PI3K/AKT/FOXO3a modulation offers insights warranting further clinical investigation. |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| sherkat.pdf | 1403/09/20 | 2315975 | دانلود |
| 787.pdf | 1403/09/20 | 253703 | دانلود |
| lin.pdf | 1403/09/20 | 825617 | دانلود |
| bartar.pdf | 1403/09/20 | 233128 | دانلود |
