خاموش سازی همزمان مولکول های CD73 و ZEB1 در سلول های سرطان سینه موشی 4T1 به منظور مهار رشد و گسترش سلول های سرطانی
Cosilencing of CD73 and ZEB1 molecules in murine 4T1 breast cancer cells in order to suppress cancer cell growth and development.
مجریان: فرهاد جدیدی نیارق
خلاصه روش اجرا: This study will be done in two phases. In the first phase we are going to sythesis our nanoparticle and in the next step after evalution of physicochemical properties of this nanoparticles, we will load this nanoparticles with siRNA. In the second phase we will evaluate effect of our treatment, nanoparticle loaded with siRNA, on breast cancer cell line, 4T1. using Real time PCR, MTT assay, Gap Closure Migration assay, colony formation and CAM assay.
اطلاعات کلی طرح 
| مرحله جاری طرح | خاتمه قرارداد و اجرا در دانشکده/مرکز |
| کد طرح | 63496 |
| عنوان فارسی طرح | خاموش سازی همزمان مولکول های CD73 و ZEB1 در سلول های سرطان سینه موشی 4T1 به منظور مهار رشد و گسترش سلول های سرطانی |
| عنوان لاتین طرح | Cosilencing of CD73 and ZEB1 molecules in murine 4T1 breast cancer cells in order to suppress cancer cell growth and development. |
| نوع طرح | طرح - پایان نامه |
| اولویت طرح | نانوفیبرها، نانوذرات و اسکافولدها (در طب بازساختی، مهندسی بافت و دارورسانی) |
| نوع مطالعه | مطالعات علوم پایه (Experimental) |
| تحقیق در نظام سلامت | بلی |
| آیا طرح پایاننامه دانشجویی است؟ | بله |
| مقطع پایان نامه | کارشناسی ارشد |
| مدت اجرا - ماه | 6 |
| نوآوری و ضرورت انجام تحقیق | We will target two molecules that are effective in tumor progression, including CD73 and ZEB1. This is while a case of this kind has not been seen before in any case. This study will be performed using synthesized nanoparticles and interventional RNAs, targeting the CD73 and ZEB1 signaling pathway. |
| اهداف اختصاصی | Generation and characterization of NPs -Impact of siRNA loaded NPs on viability of cancer cells by MTT -. Impact of siRNA loaded NPs on expression of genes involved in growth, angiogenesis , metastasis and survival of cancer cells (real time PCR) -Impact of siRNA loaded NPs on colony formation -. Impact of siRNA loaded NPs on on angiogenesis and metastasis of cancer cells (migration assay and CAM assay) |
| چکیده انگلیسی طرح | Cancer is concidered as one of the most prevalent causes of death especially in developed countries. Although several approaches have been used in order to treat cancer including, surgery, chemo-radio therapy, regardless of what advantage they have, they could not present certain cure. Thus, we need more efficient and precise approach to treat cancers. Considering that breast cancer is the second most common cancer in woman, here we will focus on this particular cancer. There are different molecules for treatment of cancerous condition. Among many options, CD73 as an enzyme that is responsible for breakdown of AMP to adenosine which is known to be expressed in cancer cell lines in abundance. Previous studies have shown that CD73 is an important monitoring molecule of cancer cells proliferation, migration, angiogenesis, metastasis and immune inhibition by cancer. Besides, Zinc finger E-box binding homeobox 1, known as ZEB1 is considered to be a transcription factor that is responsible for epithelial-to-mesenchymal transition (EMT) process. Lack of ZEB1 has been proved to be expressed in variety of cancers including breast cancer. Subsequently, ZEB1 promotes most of process involved in cancer such as migration, invasion, and metastasis. Given these molecules control similar process, targeting these two can lead to more efficient approach toward cancer treatment. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Which urges us to modify this potential therapeutic, among various suggestion, use of nanoparticles seems to be better candidate to address all these drawbacks of using siRNA at once, because nanoparticles suppress rapid degradation, since it inhibits intraction of siRNA with environment. Nanoparticle also improves cellular uptake and speciality of a treatment |
| کلمات کلیدی | CD73: CD73 molecule converts the AMP molecule into adenosine. the incidence of CD73 by tumor and host cells both play a role in tumor growth and metastasis. ZEB1: Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that modulates cell differentiation and tissue-specific functions. ZEB1 expression is implicated in the differentiation of multiple cell lineages, including bone, smooth muscle, neural, and T cells. SiRNA: (RNAi) An intervener is a term that is referred to as a duplex transcriptional duplex mechanism. In RNA-encoding technology (siRNA), the complement of the desired gene mRNA is made and this field is linked to the target gene mRNA and generates a dsRNA sequence. Because the protein synthesis system is not capable of translating two-stranded mRNA, so the expression of the target gene is stopped, and thus the gene is turned off. CD39: CD39 is the cell surface-located prototypic member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. Biological actions of CD39 are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides. This ecto-enzymatic cascade in tandem with CD73 (ecto-5–nucleotidase) also generates adenosine and has major effects on both P2 and adenosine receptor signalling. ZEB1: Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene. Adenosine: Adenosine is both a chemical found in many living systems and a medication |
| ذینفعان نتایج طرح | Cancer treatment is one of the diseases that is costly for the population and for patients, and annually leads to the exodus of the country's vast amounts to find cure for cancer treatment. Therefore, finding a method to treat this disease can have many benefits for patients, the population has a significant role in maintaining integrity. |
اطلاعات مجری و همکاران
| نام و نامخانوادگی | سمت در طرح |
|---|---|
| فرهاد جدیدی نیارق | استاد راهنمای اول (آموزشی ) |
| مهدی یوسفی | مشاور |
| بهزاد برادران | مشاور |
| افشین نیک خو | دانشجوی مالک پایان نامه |
| خالد عوده الزاملی | دانشجوی مالک پایان نامه |
اطلاعات تفضیلی
| حوزه خبر | خبر |
|---|---|
| رسانه ها و مردم | عنوان خبر متن خبر |
| متخصصان و پژوهشگران | عنوان خبر مهار همزمان مولکول های CD73 و ZEB1 مانع رشد سرطان می شود.متن خبر بیان غیرعادی چندین عامل در محیط تومور به پیشرفت نئوپلازی و سرکوب سیستم ایمنی در سرطان های مختلف کمک می کند. ZEB-1 و CD73 فاکتورهای مهمی در پیشرفت تومور هستند ، که بیان بیش از حد آنها در محل تومور، چندین ویژگی مشخص در سرطان را افزایش می دهد، از جمله تکثیر، رگ زایی، متاستاز، مهاجرت و حمله.
در این مطالعه ، ما تصمیم گرفتیم با استفاده از نانوذرات لاکتات کیتوزان متصل به RGD (RGD-CL) (NPs) محصور کننده مولکول های CD73 / ZEB-1 siRNA ، in vitro و in vivo از بیان این عوامل در سایت تومور جلوگیری کنیم.
نتایج نشان داد که NP های متصل به RGD می توانند به طور م cellsثر سلولهای سرطانی را از طریق برهم کنش با αvβ3 اینتگرینهای بیان شده در سلولهای سرطانی و سلولهای اندوتلیال تومور ، ترانسفکت کنند و منجر به سرکوب مولکولهای هدف و کاهش رشد سلولهای سرطانی ، در شرایط in vitro شوند. علاوه بر این ، تجویز این NP ها به رگرسیون تومور و رگ زایی ضعیف در تخمدان منجر شد.
این یافته ها اهمیت هدف گیری ترکیبی CD73 و ZEB-1 را در درمان سرطان به زودی در بیماران سرطانی برجسته می کند. |
| سیاستگذاران درمانی | عنوان خبر متن خبر |
| سیاستگذاران پژوهشی | عنوان خبر متن خبر |
| لینک (URL) مقاله انگلیسی مرتبط منتشر شده 1 |
