اثرات ضد توموری ترکیبی از اسانس سیلیبیوم مارانوم و 5-فلورویوراسیل بر سلول‌های کبدی (HepG2)

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه باغبانی، واحد اهواز، دانشگاه آزاد اسلامی، اهواز، ایران

2 استاد مدعو گروه باغبانی، واحد اهواز، دانشگاه آزاد اسلامی، اهواز، ایران و عضو هیئت علمی گروه علوم باغبانی، دانشکده کشاورزی، دانشگاه علوم کشاورزی و منابع طبیعی خوزستان، اهواز، ایران

3 استاد مدعو گروه باغبانی، واحد اهواز، دانشگاه آزاد اسلامی، اهواز، ایران و عضو هیئت علمی مرکز تحقیقات بیوشیمی و تغذیه در بیماریهای متابولیک، دانشگاه علوم پزشکی کاشان، کاشان، ایران

چکیده

د
سرطان سلول‌های کبدی (HCC) یکی از شایع‌ترین بدخیمی‌ها در سرتاسر جهان می‌باشد و نسبت به  داروهای شیمی‌درمانی مانند دوکسوروبیسین و 5-فلورویوراسیل (5-FU) مقاوم می‌باشد. عصاره سیلیبیوم ماریانوم یا ترکیب فعال سیلی مارین آن خاصیت ضدسرطانی دارد و بپیشنهاد شده است که به عنوان یک عامل جایگزین و مکمل در درمان می‌تواند استفاده می شود. در این مطالعه تأثیرات ترکیبی اسانس سلیبیوم ماریانوم و5-FU برای سرکوب رشد HCC در شرایط آزمایشگاهی با تأثیر بر مسیرهای Wnt، NF-κB، رگ‌زائی، آپوپتوز و اتوفاژی بررسی شد. بیان ژن‌های مسیر پیام­رسانی NF-κB و Wnt و همچنین فاکتورهای مربوط به رگ‌زائی، آپوپتوز و اتوفاژی با استفاده از تکنیک‌های وسترن بلات و qRT-PCR بررسی شد. براساس نتایج بدسن آمده همه تیمارها در مقایسه با گروه کنترل، زیستاییِ سلول‌های HepG2 را کاهش دادند. علاوه بر این، اسانس سلیبیوم ماریانوم خوزستان یا اصفهان (Sm-K و Sm-I) در ترکیب با 5-FU، مهاجرت و تهاجم را در سلول‌های HepG2 را کاهش داد. از لحاظ آماری میانگین بیان پروتئین‌های مرتبط با رگ‌زائی (VEGF، COX-2، Bfgf و HIF-1α)، آپوپتوز (Bcl-2، Bax و کاسپاز-8)، اوتوفاژی (Beclin-1، LC3-I و LC3-II) و NF-kB (total NF-κB (p65) و phospho NF κB (p65)) به میزان قابل توجهی در سلول­های تیمار شده در مقایسه با گروه کنترل تغییر یافته است. علاوه براین، سطوح بیان ژن‌های مرتبط با مسیر Wnt نیز کاهش یافت. روی هم رفته، یافته‌ها نشان داد که سلیبیوم ماریانوم به تنهایی یا در ترکیب با 5-FU می‌تواند از طریق تنظیم مسیرهای پیام­رسانی اتوفاژی، آپوپتوز، رگ‌زائی، NF κB و Wnt، اثرات ضدتومور ایجاد کند.

کلیدواژه‌ها


عنوان مقاله [English]

Anti-tumor effects of Silybum marianum essential oil and 5-fluorouracil combination on Hepatocellular carcinoma cells (HepG2)

نویسندگان [English]

  • Mohammad Jaber Masoud Khooy 1
  • Mohammadreza Salehi Salmi 2
  • Massoumeh Farasat 1
  • Hamed Mirzaei 3
1 Department of Horticulture, Ahvaz Islamic Azad University, Science and Research Branch, Ahvaz, Iran
2 Visiting Professor, Department of Horticulture, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran and Faculty Member, Department of Horticulture, Faculty of Agriculture, Khuzestan University of Agricultural Sciences and Natural Resources, Ahvaz, Iran
3 Visiting Professor, Department of Horticulture, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran and Faculty Member of Biochemistry and Nutrition Research Center in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
چکیده [English]

The present study evaluated the efficacy of combining 5-fluorouracil (5-FU) and Silybum marianum essential oils to suppress in vitro Hepatocellular carcinoma (HCC) growth by influencing the Wnt, NF-κB, angiogenesis, apoptosis and autophagy pathways. Silybum marianum essential oils were studied alone and in combination with 5-FU in the HepG2 cell-line. The expression of NF-κB and Wnt signaling pathway genes as well as angiogenesis-, apoptosis- and autophagy-associated genes and proteins were evaluated using Western blot and qRT-PCR techniques. Each treatment decreased the viability of HepG2 cells compared with the control group. Moreover, S. marianum essential oils from Khozestan or Isfahan (Sm-K and Sm-I) in combination with 5-FU reduced the migration and invasion of HepG2 cells. Angiogenesis-related proteins i.e. VEGF, COX-2, Bfgf and HIF-1α were significantly reduced. Apoptosis- and autophagy-related proteins i.e. caspase-8, Bax, Bcl-2, Beclin-1, LC3-I, and LC3-II were modulated by each treatment. Each treatment decreased total NF κB (p65) and phospho NF κB (p65) at protein levels. The expression levels of Wnt pathway-related genes were also decreased. Taken together, these findings revealed that S. marianum, either alone or in combination with 5-Fu, could exert anti-tumor effects via modulating autophagy, apoptosis, angiogenesis, NF κB and Wnt signaling pathways.

کلیدواژه‌ها [English]

  • angiogenesis
  • hepatocellular carcinoma
  • Silybum marianum essential oil
  • 5-Fluorouracil
  • Combination therapy
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