بررسی خاصیت ضد سرطانی و تنظیم کنندگی سیستم ایمنی سلول‌های سرطانی Hela تیمار شده با پپتید HL-10 در شرایط برون تنی و درون تنی

محورهای موضوعی : فصلنامه زیست شناسی جانوری

مریم رضاوند ¹ , زهرا ستایش مهر ^{2 *} , فاطمه حدادی ³

1 - گروه زیست شناسی، دانشکده علوم پایه، دانشگاه زابل، زابل، ایران
2 - گروه زیست شناسی، دانشکده علوم پایه، دانشگاه زابل، زابل، ایران
3 - گروه زیست شناسی، دانشکده علوم پایه، دانشگاه زابل، زابل، ایران

تاریخ دریافت : 1403/02/28 تاریخ پذیرش : 1403/06/08 تاریخ انتشار : 1404/03/06

کلید واژه: پپتید, سرطان, آپپتوز, فاکتور التهابی, سیستم ایمنی,

چکیده مقاله :

در این مطالعه خاصیت ضد سرطانی، تنظیم کنندگی سیستم ایمنی و همچنین اثر پپتید HL-10 بر مسیر سیگنال‌دهی آپوپتوز با اندازه‌گیری بیان ژن­های Bcl-2، Cytochrome c و Bim بررسی شد. سلول‌های سرطان دهانه رحم HeLa  با پپتید HL-10 در غلظت­های مختلف و زمان‌های 24 و 48 ساعت تیمار شدند. به منظور ارزیابی اثرات درون تنی پپتید HL-10، سرطان  دهانه رحم در موش balb-c القا شد. سپس، سطوح IFN-γ و IL-4 سرم، با استفاده از ELISA اندازه گیری شد. سمیت و درصد بقای سلولی، بیان ژن‌های Bim، Cytochrome c و Bcl-2 سلول‌ها و تومور تیمار شده با پپتید HL-10 به روش Real Time PCR بررسی شد. پپتید HL-10  زنده‌مانی سلول‌هایHeLa  را به صورت وابسته به غلظت و زمان کاهش می‌دهد. مقدار IC50 برای پپتید HL-10 در زمان 24 ساعت، 49/18میکرومولار و در زمان 48 ساعت، 62/30 میکرومولار بدست آمد. نتایج نشان داد که پپتید HL-10 تأثیر معنی‌داری بر بیان ژن‌های مورد مطالعه داشت. پپتید Hl-10 باعث افزایش  در بیان ژن BIM و Cytochrome c و کاهش بیان ژن Bcl-2 در سلول‌های سرطانی درمان شده با پپتید HL-10 در مقایسه با سلول‌های درمان نشده در شرایط درون تنی و برون تنی شد. همچنین، نتایج نشان داد که غلظت فاکتورهای التهابی INF- γ ، IL-1β و IL-6 در سرم موش­های سرطانی بدون تیمار (Sham) نسبت به موش­های سالم بدون تیمار (NC) کاهش معنادار، در حالیکه غلظت IL-4 افزایش نشان داد (05/0 p <).  احتمالاً پپتید HL-10 در مسیرهای ذاتی آپوپتوز و همچنین در تنظیم سیستم ایمنی نقش دارد. به نظر می رسد پپتید HL-7 می­تواند یک کاندید مناسب و امیدوارکننده برای درمان سرطان دهانه رحم باشد.

چکیده انگلیسی:

The present study aimed to assess the anti-cancer properties, immune system regulation, and apoptosis signaling pathway impact of the HL-10 peptide through gene expression analysis of Bcl-2, Cytochrome c, and Bim. HeLa cervical cancer cells were subjected to treatment with HL-10 peptide for both 24 and 48 hours at varying concentrations. To assess the in vivo impacts of the HL-10 peptide, BALB-c mice were infected with cervical cancer. Serum levels of IFN-β and IL-4 were subsequently quantified via ELISA. Using real-time PCR, the expression of the genes Bim, Cytochrome c, and Bcl-2 in cells and tumors treated with the HL-10 peptide was analyzed, along with the percentage of viable cells and toxicity. The HL-10 peptide decreases the survival rate of HeLa cells in a way that is dependent on both the concentration and duration of exposure. The HL-10 peptide exhibited an IC50 value of 18.49 μM after 24 hours and 30.62 μM after 48 hours. The findings demonstrated that the HL-10 peptide exerted a significant impact on the expression of the investigated genes. The HL-10 peptide upregulated the expression of the BIM and Cytochrome c genes while downregulating the expression of the Bcl-2 gene in cancer cells treated with the HL-10 peptide, both in vitro and in vivo. The results indicated a significant decrease in the quantity of inflammatory components INF-γ, IL-1β, and IL-6 in the serum of untreated cancer mice (Sham) compared to untreated healthy mice (NC). Conversely, there was a significant rise in the concentration of IL-4 (p < 0.05). The HL-10 peptide likely functions in the modulation of the immune system and in the intrinsic pathways of apoptosis. The HL-7 peptide appears to be a viable and auspicious candidate in the realm of cervical cancer treatment.

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