اثرات ضدگلیوبلاستومای نانومیسل‌کورکومین همراه با ارلوتینیب در سلول‌های گلیوبلاستومای انسانی U87

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه زیست شناسی، واحد دامغان، دانشگاه آزاد اسلامی، دامغان، ایران

2 مرکز تحقیقات بیوشیمی و تغذیه در بیماری های متابولیک، دانشگاه علوم پزشکی کاشان، کاشان، ایران

چکیده

گلیوبلاستوما (GBM) یکی از مهمترین نئوپلاسم‌های مغزی است و با مقاومت دارویی بالا همراه است. مکانیسم‌های مختلف سلولی و مولکولی، از جمله آپوپتوز، آنژیوژنز، اتوفاژی، مسیرهای NF-κB و Wnt، نقش مهمی در پیشرفت GBM ایفا می‌کنند. ما در این مطالعه، اثر کورکومین و نانومیسل‌کورکومین همراه با ارلوتینیب را برای سرکوب GBM در شرایط آزمایشگاهی بررسی کردیم. این سرکوب با تأثیر بر مسیرهای سیگنالینگ NF-kB و Wnt، مهار آنژیوژنز و القای اتوفاژی و آپوپتوز انجام می‌شود. کورکومین و نانومیسل‌کورکومین (50 میکرومولار) به تنهایی و همراه با ارلوتینیب (50 میکرومولار) در سلولهای گلیوبلاستوما U87 بررسی شد. بیان مسیرهای سیگنالینگ Wnt و NF-kB، آپوپتوز، آنژیوژنز، ژن‌ها و پروتئین‌های مرتبط با اتوفاژی توسط qRT-PCR و وسترن بلات بررسی شد. در مقایسه با گروه کنترل، تمام تیمارها از زیستایی سلولهای گلیوبلاستومای U87 کاسته‌اند. علاوه بر این، پروتئین‌های مرتبط با آنژیوژنز، به عنوان مثال، Cox-2، VEGF، HIF-1α و bFGF، به طرز چشمگیری کاهش یافته‌اند. همه تیمارها پروتئین‌های مرتبط با اتوفاژی و آپوپتوز، یعنی Bax، Beclin 1، کاسپاز 8، Bcl-2، LC3-II و LC3-I را تنظیم کردند. Total NF κB (p65) و phospho NF. κB (p65) با هر تیمار در سطح پروتئین کاهش یافتند. بیان VEGF، cyclin D1، Twist، ZEB و ژن‌های مرتبط با مسیر Wnt نیز کاهش یافت. به طور کلی، این نتایج نشان داد که کورکومین و نانومیسل‌کورکومین به تنهایی یا در ترکیب با ارلوتینیب از طریق تنظیم یک سری مکانیسم‌ها مانند آپوپتوز، اتوفاژی، آنژیوژنز، مسیرهای سیگنالینگ Wnt و NF. κB‌، اثرات ضد GBM از خود نشان می‌دهند.

کلیدواژه‌ها

عنوان مقاله [English]

Anti-glioblastoma Effects of Nano-micelle Curcumin Plus Erlotinib

نویسندگان [English]

  • Ali Bagherian 1
  • Hamed Mirzaei 2
  • Nahid Masoudian 1
  • Bostan Roudi 1
1 Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
2 Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
چکیده [English]

Glioblastoma is one of the most dangerous types of brain cancer, with a high rate of therapy resistance. Apoptosis, angiogenesis, autophagy, NF-κB, and Wnt pathways are just a few of the molecular and cellular processes that play a role in Glioblastoma development. The effectiveness of curcumin and Nano-micell curcumin with Erlotinib to suppress Glioblastoma in vitro was investigated in this study.The suppression is carried out by affecting NF-κB and Wnt signaling pathways, angiogenesis inhibition, and autophagy and apoptosis induction. Curcumin and Nano-micelle Curcumin (50 μM) was investigated alone and with Erlotinib (50 μM) in the U87 glioblastoma cells. The expression of Wnt and NF-κB signaling pathways, apoptosis, angiogenesis, and autophagy-related genes and proteins were assessed by qRT-PCR and Western blot. Compared with the control group, all treatments declined the U87 glioblastoma cells viability. Furthermore, Angiogenesis-associated proteins, i.e., Cox-2, VEGF, HIF-1α & bFGF, were remarkably decreased. Each treatment regulated autophagy and apoptosis-associated proteins, i.e., Bax, Beclin 1, caspase 8, Bcl-2, LC3-II, and LC3-I. Total NF κB (p65) and phospho NF. κB (p65) declined by each treatment at protein levels. Expressions of VEGF, cyclin D1, Twist, ZEB, and Wnt pathway-associated genes were also decreased. In general, our findings demonstrated that curcumin and Nano-micelle Curcumin, either alone or in conjunction with Erlotinib, had anti-Glioblastoma effects via modulating a number of processes including apoptosis, autophagy, angiogenesis, Wnt, and NF. κB signaling pathways.
 

کلیدواژه‌ها [English]

  • Erlotinib
  • Curcumin
  • Nano-micelle Curcumin
  • Glioblastoma

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فصلنامه زیست شناسی جانوری
دوره 14، شماره 2
دی 1400
صفحه 211-229

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