مجله علوم پزشکی پارس

تغییرات بیانی ژن CD44 و افزایش میزان آپوپتوز در رده سلولی MCF-7 سرطان پستان در شرایط بی‌وزنی شبیه سازی شده

نویسندگان

استادیار پژوهشی، دکتری تخصصی، پژوهشگاه هوافضا، وزارت علوم تحقیقات و فناوری

چکیده

مقدمه: مولکول CD44 در چسبندگی سلولی، هدایت رشد و مسیرهای سیگنالی سلول نقش داشته و در بسیاری از انواع سرطان ها از جمله سرطان پستان دخالت دارد، به گونه ای که بیان آن در تومورهای بازال تهاجمی بسیار زیاد است.  بی وزنی شبیه سازی شده بر تکثیر و متاستاز سلول های توموری اثر می گذارد و درسال های اخیر به عنوان یک روش جدید برای مطالعه رشد و تکثیر سلول های سرطانی معرفی شده است. هدف از مطالعه حاضر بررسی بیان ژن CD44 و میزان آپوپتوز در رده سلولی MCF-7 سرطان پستان در شرایط بی‌وزنی شبیه سازی شده بود.
روش کار: رده سلولی MCF-7 در شرایط جاذبه طبیعی و بی‌وزنی (1 و 3 روز) توسط دستگاه کلینواستت تکثیر شد. بیان ژن و میزان آپوپتوز با استفاده از روش Real-time PCR و کیت رنگ آمیزی انکسین 5 اندازه‌گیری شد.
یافته ها: نتایج نشان داد که میزان بیان ژن پس از یک روز بیان ژن را 50 درصد کاهش و پس از 3 روز به میزان 4 برابر افزایش می دهد. همچنین میزان آپوپتوز به میزان 40 درصد پس از یک روز بی‌وزنی افزایش یافت.
نتیجه‌گیری: به نظر می‌رسد که پاسخ سلول‌های سرطانی به بی‌وزنی می‌تواند وابسته به زمان باشد و اعمال بی‌وزنی روی رده سلولی MCF-7 برای مدت یک روز می تواند اثرات مثبتی بر کاهش فنوتیپ سرطانی در این رده سلولی داشته باشد و بتواند به عنوان روشی جدید برای درمان سرطان مورد توجه قرار بگیرد.

کلیدواژه‌ها

عنوان مقاله [English]

CD44 expression changes and increased apoptosis in MCF-7 cell line of breast cancer in simulated microgravity condition

نویسندگان [English]

  • Zahra Hajebrahimi
  • Maryam Salavatifar

Aerospace Research Institute, Ministry of Science Research and Technology, Tehran, Iran

چکیده [English]

Introduction: CD44 molecule plays a role in cell adhesion and conduction of growth and cell signaling pathways and
is involved in many types of cancers including breast cancer, which is highly expressed in invasive basal tumors. Simulated microgravity (weightlessness) affects tumor cell proliferation and metastasis and has been introduced in recent years as a new method to study the growth and proliferation of cancer cells. Therefore, the aim of the present study was to investigate the gene expression of CD44 and the level of apoptosis in MCF-7 breast cancer cell line under simulated microgravity condition.
Materials and Methods: MCF-7 cell line was proliferated under normal gravity and microgravity (1 and 3 days) using clinostat apparatus. Gene expression and apoptosis was measured using real-time PCR technique and Annexin
V staining kit.
Results: The results showed that microgravity reduce gene expression (50%) after 1 day and increased it four times after 3 days. Also, the level of apoptosis was increased 40% after 1 day of microgravity.
Conclusion: It seems that the response of cancer cells to microgravity can be time dependent and microgravity
treatment for 1 day on MCF-7 cell line may have positive effects on reducing the phenotype of cancer in this cell line and can consider as a new way for cancer therapy.

کلیدواژه‌ها [English]

  • Breast Cancer
  • Weightlessness
  • CD44
  • Apoptosis
1- Naor D, Sionov RV, Ish-Shalom D. CD44: structure, function, and association with the malignant process. Adv Cancer Res 1997; 71: 241–319. 2- Naor D, Nedvetzki S, Golan I, Melnik L, Faitelson Y. CD44 in cancer. Crit Rev Clin Lab Sci 2002; 39 (6): 527–79. 3- Gao AC, Lou W, Dong JT, Isaacs JT. CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res 1997; 57 (5): 846–9. 4- Horak CE, Lee JH, Marshall JC, Shreeve SM, Steeg PS. The role of metastasis suppressor genes in metastatic dormancy. APMIS 2008; 116 (7-8): 586–601. 5- Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 2011; 17 (2): 211–5. 6- Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100 (7): 3983–8. 7- Yu Q, Stamenkovic I. Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev 1999; 13 (1): 35–48. 8- Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 2000; 14 (2): 163–76. 9- Ghatak S, Misra S, Toole BP. Hyaluronan oligosaccharides inhibit anchorage-independent growth of tumor cells by suppressing the phosphoinositide 3-kinase/Akt cell survival pathway. J Biol Chem 2002; 277 (41): 38013–20. 10- Williams D, Kuipers A, Mukai C, Thirsk R. Acclimation during space flight: effects on human physiology. CMAJ. 2009; 180 (13): 1317–23. 11- Moos PJ, Fattaey HK, Johnson TC. Cell proliferation inhibition in reduced gravity experimental cell research 1994, 213 (2): 458-462. 12- Jessup JM, Goodwin TJ, Spaulding G. Prospects for use of microgravity-based bioreactors to study three-dimensional host tumor interactions in human neoplasia. J Cell Biochem 1993; 51 (3): 290–300. 13- Hughes-Fulford M. Function of the cytoskeleton in gravisensing during spaceflight. Adv Space Res 2003; 32 (8); 1585–1593. 14- Infanger M, Kossmehl P, Shakibaei M, Bauer J, Kossmehl-Zorn S, Cogoli A, et al. Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells. Cell Tissue Res 2006; 324: (2), 267-77. 15- Guignandon A, Usson Y, Laroche N, Lafage-Proust MH, Sabido O, Alexandre C, et al. Effects of intermittent or continuous gravitational stresses on cell–matrix adhesion: quantitative analysis of focal contacts in osteoblastic ROS 17/2.8 cells. Exp Cell Res 1997; 236 (1): 66–75. 16- Vassy J, Portet S, Beil M, Millot G, Fauvel-Lafève F, Gasset G, et al. Weightlessness acts on human breast cancer cell line MCF-7. Adv Space Res 2003; 32 (8): 1595–1603. 17- Chang D, Xu H, Guo Y, Jiang X, Liu Y, Li K, et al. Simulated microgravity alters the metastatic potential of a human lung adenocarcinoma cell line. In Vitro Cell Dev Biol Anim 2013; 49 (3): 170–177. 18- Ryu HW, Choi SH, Namkoong S, Jang IS, Seo DH, Choi I, et al. Simulated microgravity contributes to autophagy induction by regulating AMP-activated protein kinase. DNA Cell Biol 2014; 33 (3): 128–135. 19- Wickstead B, Gull K. The evolution of the cytoskeleton. J Cell Biol 2011; 194 (4): 513–525. 20- Tan X, Xu A, Zhao T, Zhao Q, Zhang J, Fan C, et al. Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways. Sci Reports 2018; 8 (1): 3769-80. 21- Prat A, Karginova O, Parker JS, Fan C, He X, Bixby L, et al. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes. Breast Cancer Res Treat 2013; 142 (2): 237-255. 22- Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008; 10 (2): R25-37. 23- Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, et al. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 2006; 8 (5): R59-71. 24- Bayliss J, Hilger A, Vishnu P, Diehl K, El-Ashry D. Reversal of the estrogen receptor negative phenotype in breast cancer and restoration of antiestrogen response. Clin Cancer Res 2007; 13(23): 7029-7036. 25- Ricardo S, Filipe Vieira A, Gerhard R, Leitão D, Pinto R, Cameselle-Teijeiro JF, et al. Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol 2011; 64 (11): 937-946. 26- Reed JC. Apoptosis-based therapies. Nat Rev Drug Discov 2002; 1 (2): 111-21.
مجله علوم پزشکی پارس
دوره 17، شماره 3 - شماره پیاپی 49
مهر 1398
صفحه 26-34