درک مسیرهای مختلف مرگ برنامه ریزی شده سلولی در درمان هدفمند بیماری ها
محورهای موضوعی : زیست شناسی سلولی تکوینی گیاهی و جانوری ، تکوین و تمایز ، زیست شناسی میکروارگانیسم
امیر آراسته
1
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مرتضی کریم پور
2
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فائزه فلاح
3
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سارا کیانی
4
1 - گروه زیست شناسی، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران
2 - گروه زیست شناسی، دانشگاه آزاد اسلامی واحد رشت
3 - گروه زیست شناسی، واحد تهران مرکزی، دانشگاه آزاد اسلامی، تهران، ایران
4 - گروه زیست شناسی، واحد تهران مرکزی، دانشگاه آزاد اسلامی، تهران، ایران
کلید واژه: کلمات کلیدی: آپوپتوز, مسیرهای پیام رسانی, کاسپاز, سرطان,
چکیده مقاله :
چکیده ایجاد درمان¬هایی که مرگ کارآمد سلول¬های سرطانی توسط آپوپتوز را تشویق می¬کند، سنگ بنا و هدف انکولوژی بالینی برای بیش از سی سال بوده است. مسیرهای پیام رسانی متعددی که به¬عنوان درونی و بیرونی شناخته می¬شوند، در فرآیند مرگ برنامه ریزی شده سلولی نقش دارند. این مسیرها توسط محرک-های مختلفی مانند نظارت بر سیستم ایمنی، آسیب DNA و استرس سلولی فعال می¬شوند. مرگ سلولی همچنین ممکن است تحت تأثیر نحوه تعامل مسیرهای آپوپتوز با سایر فرآیندهای پیام رسانی قرار گیرد. مطالعات کشف دارو (با پرداختن به فراهمی زیستی، پایداری، نفوذ تومور، مشخصات سمیت در بافت‌های غیر بدخیم، تداخلات دارویی، و اثرات خارج از هدف) و درک بیولوژی تومور برای ترجمه بالینی عوامل موثر بر آپوپتوز ضروری است. مرگ سلولی تومور با روش¬های درمانی امکان پذیر است، اما انتخاب، رشد و پراکندگی سلول¬های مقاوم به درمان در نهایت پتانسیل کشندگی را تعیین می کند. هدف از مطالعه حاضر بررسی مسیرهای آپوپتوز اولیه و مسیرهای پیام رسانی مرتبط با آن، به همراه بحث در مورد اهداف مولکولی آن¬ها از منظر درمانی بوده است.
Abstract Developing therapies that promote the efficient death of cancer cells by apoptosis has been a cornerstone and goal of clinical oncology for over thirty years. Multiple signaling pathways, known as intrinsic and extrinsic, are involved in the process of programmed cell death. These pathways are activated by various stimuli such as immune surveillance, DNA damage and cellular stress. Cell death may also be influenced by how apoptotic pathways interact with other signaling processes. Drug discovery studies (Addressing bioavailability, stability, tumor penetration, toxicity profile in non-malignant tissues, drug interactions, and off-target effects) and an understanding of tumor biology are essential for the clinical translation of effective pro-apoptotic agents. Tumor cell death is possible with therapeutic methods, but the selection, growth and proliferation of resistant cells ultimately determine the lethality potential. The present study aimed to investigate the early apoptosis pathways and the related signaling pathways, along with discussing their molecular targets in terms of therapy.
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