مشاهده اثرات ضد سرطانی آفلاتوکسین B1 در تومور پستانی رده 4T1 موش با تزریق اطراف توموری

نویسندگان

1 دانش آموخته قارچ شناسی دامپزشکی واحد علوم و تحقیقات، دانشگاه آزاد اسلامی،تهران، ایران

2 گروه پاتوبیولوژی ، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی،تهران، ایران

3 گروه علوم درمانگاهی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران

4 گروه انگل شناسی و قارچ شناسی ،دانشکده بهداشت ، دانشگاه علوم پزشکی دانشگاه تهران، تهران، ایران

چکیده

درمان سرطان پستان به دلیل اثرات سیستمیک شیمی درمانی دارای مشکلات زیادی است. استفاده از برخی مولکول ها با اثرات سلول کشی مثل آفلاتوکسین B1، می تواند اثرات مهلک روی سلول های سرطان پستان داشته باشد. در این مطالعه، اثر مهاری استفاده موضعی آفلاتوکسین B1 برروی سرطان پستان را بررسی کردیم. سلول های سرطانی رده 4T1 به صورت زیر جلدی در موش های ماده تلقیح شدند. سپس دوز های 50 و 500 میکروگرم بر میلی لیتر از آفلاتوکسین B1 در مقایسه با دوکسوروبیسین در اطراف تومورها تزریق گردید. ارزیابی نسبت اندازه تومور به وزن حیوان در گروه های مختلف همراه با انجام هیستوپاتولوژی به روش ایمنوفلورسانس روی شاخص Ki-67  و VEGF صورت گرفت. آفلاتوکسین B1 به طور معنی داری باعث کوچک شدن حجم، نکروز و سرکوب رگزایی در تومور می شود. با این وجود، متاستاز کبدی در همه گروه ها اتفاق افتاد. آفلاتوکسین B1 در تزریق موضعی 50 و 500 میکروگرم بر میلی لیتر در اطراف تومور دارای اثرات ضد سرطانی پستان است. ولی نمی تواند مانع وقوع متاستاز شود.همچنین هپاتوتوکسیسیتی ناشی از سم آفلاتوکسین نیز مشاهده گردید.اثرات و بررسی اثرات در یک مطالعه تجربی صورت می گیرد.

کلیدواژه‌ها


عنوان مقاله [English]

Observation of anti-cancer effects of aflatoxin B1 in breast tumor category 4T1 of mice by injection around the tumor

نویسندگان [English]

  • R. Mousazadeh, 1
  • S. Hesaraki, 2
  • M. Bayat, 2
  • A. Jahandideh, 3
  • J. Hashemi, 4
1 Graduated from Faculty of Veterinary Medicine, Sciences and Research Branch, Islamic Azad University, Tehran, Iran
2 Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 Department of Clinical Sciences, Sciences and Research Branch, Islamic Azad University, Tehran, Iran
4 Department of Parasitology and Mycology, School of Health University of Medical Sciences University of Tehran, Tehran, Iran
چکیده [English]

Treatment of breast cancer has many problems due to the systemic effects of chemotherapy. The use of certain molecules with cell killing effects, such as aflatoxin B1, can have fatal effects on breast cancer cells. In this study, we investigated the inhibitory effect of topical aflatoxin B1 use on breast cancer. Class 4T1 cancer cells were inoculated subcutaneously in female mice. Doses of 50 and 500 μg / ml of aflatoxin B1 were then injected around the tumors in comparison with doxorubicin. The ratio of tumor size to animal weight in different groups was evaluated along with histopathology by immunofluorescence on Ki-67 and VEGF indices. Aflatoxin B1 significantly reduces tumor volume, necrosis and suppresses angiogenesis in the tumor. However, liver metastasis occurred in all groups. Aflatoxin B1 in topical injections of 50 and 500 μg / ml around the tumor has anti-cancer effects on the breast. But it can not prevent metastasis.Aflatoxin-induced hepatotoxicity was also observed.

  1. Siegel R, Brawley O. cancer statistics. 2011: the impact of eliminating socioeconomic  and racial disparities on premature cancer deaths .CA cancer j clin.2011:61(4)212-36.
  2. Nafissi N, Saghafinia M, Akbari  ME . A survey of breast cancer knowledge and attitude in  Iranian women . J Cancer Res Ther.2012; 8(1):46-9.
  3. Banegas MP, Bird Y, Moravos J. Breast cancer knowledge.attitudes  and early detection practices in United States-Mexico  border Latinas. J Womens  Healt .2012;21(1):101-7.
  4. Ferlay JS, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1. 0. Cancer incidence and mortality worldwide: IARC CancerBase. 2013;11.
  5. Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF. A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiology and Prevention Biomarkers. 1999 Oct 1;8(10):843-54.
  6. Shantakumar S, Terry MB, Teitelbaum SL, Britton JA, Millikan RC, Moorman PG, Neugut AI, Gammon MD. Reproductive factors and breast cancer risk among older women. Breast cancer research and treatment. 2007 May;102(3):365-74.
  7. Paffenbarger Jr RS, Kampert JB, Chang HG. Characteristics that predict risk of breast cancer before and after the menopause. American Journal of Epidemiology. 1980 Aug 1;112(2):258-68.
  1. Meki A, El-Gibaly I. Melatonin reduces apoptosis rate induced by aflatoxin B1 in rat liver. Neuroendocrinology letters.2001;22:417-426.
  1. Mazdak Razi , Shapour Hassanzadeh , Toraj  Zamir  Nasta . Effect of Aflatoxin B1 on Histo morphometric  Parameters  of Testis in Male Mature Albino Mouse. Qom  Uni  Med Sci  2017 March
  2. Zhang YJ, Chen Y, Ahsan H, Lunn RM, Lee PH, Chen CJ, et al. Inactivation of the DNA repair gene O6‐methylguanine‐DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1‐DNA adducts and p53 mutation in hepatocellular carcinoma. International journal of cancer. 2003;103(4):440-4.
  3. Yousefi F, Siadat SD, Saraji AA, Hesaraki S, Aslani MM, Mousavi SF, et al. Tagging staphylococcal enterotoxin B (SEB) with TGFaL3 for breast cancer therapy. Tumor Biology. 2016;37(4):5305-16.
  4. Xu J, Koizumi K, Liu M, Mizuno Y, Suzaki M, Iitsuka H, et al. Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis. Oncology reports. 2019;41(3):2020-6.
  5. Xin Y-F, Wan L-L, Peng J-L, Guo C. Alleviation of the acute doxorubicin-induced cardiotoxicity by Lycium barbarum polysaccharides through the suppression of oxidative stress. Food and Chemical Toxicology. 2011;49(1):259-64.
  6. King PD, Perry MC. Hepatotoxicity of chemotherapy. The oncologist. 2001;6(2):162-76.
  7. Gao ZG, Tian L, Hu J, Park IS, Bae YH. Prevention of metastasis in a 4T1 murine breast cancer model by doxorubicin carried by folate conjugated pH sensitive polymeric micelles. J Control Release. 2011;152(1):84-9.
  8. De Francesco EM, Lappano R, Santolla MF, Marsico S, Caruso A, Maggiolini M. HIF-1α/GPER signaling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs). Breast Cancer Research. 2013;15(4):1-18.
  9. Shi Y, Tong M, Wu Y, Yang Z, Hoffman RM, Zhang Y, et al. VEGF-C ShRNA inhibits pancreatic cancer growth and lymphangiogenesis in an orthotopic fluorescent nude mouse model. Anticancer research. 2013;33(2):409-17.
  10. Ruggeberg K-G, O’Sullivan P, Kovacs TJ, Dawson K, Capponi VJ, Chan PP, et al. Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B 1. Scientific reports. 2020;10(1):1-13.
  11. Bent R, Moll L, Grabbe S, Bros M. Interleukin-1 beta—a friend or foe in malignancies? International journal of molecular sciences. 2018;19(8):2155.
  12. Sato T, Terai M, Tamura Y, Alexeev V, Mastrangelo MJ, Selvan SR. Interleukin 10 in the tumor microenvironment: a target for anticancer immunotherapy. Immunologic research. 2011;51(2):170-82.
  13. Meiyanto E, Putri H, Larasati YA, Utomo RY, Jenie RI, Ikawati M, et al. Anti-proliferative and anti-metastatic potential of curcumin analogue, pentagamavunon-1 (PGV-1), toward highly metastatic breast cancer cells in correlation with ROS generation. Advanced pharmaceutical bulletin. 2019;9(3):445.
  14. Mohamad NE, Yeap SK, Abu N, Lim KL, Zamberi NR, Nordin N, et al. In vitro and in vivo antitumour effects of coconut water vinegar on 4T1 breast cancer cells. Food & nutrition research. 2019;63.
  15. Qin N, Lu S, Chen N, Chen C, Xie Q, Wei X, et al. Yulangsan polysaccharide inhibits 4T1 breast cancer cell proliferation and induces apoptosis in vitro and in vivo. International journal of biological macromolecules. 2019;121:971-80.
  16. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nature reviews cancer. 2008;8(8):579-91.
  17. Ribeiro DH, Ferreira FL, Da Silva VN, Aquino S, Corrêa B. Effects of aflatoxin B1 and fumonisin B1 on the viability and induction of apoptosis in rat primary hepatocytes. International journal of molecular sciences. 2010;11(4):1944-55.
  18. Chen K, Shu G, Peng X, Fang J, Cui H, Chen J, et al. Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B1. Food and chemical toxicology. 2013;59:446-54.

27.       Wang F, Xu P, Xie KC, Chen XF, Li CY, Huang Q. Effects of tumor microenviromental factors on VEGF expression. Biomedical reports. 2013;1(4):539-44.