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ELT-2017 Inhibits Tumour Growth and Prevents Triple Negative Breast Cancer Invasion in Model Systems through Dysregulation of Ran-GTP

المؤلف الرئيسي: Al-Ramamneh, Rahmeh Saad (Author)
مؤلفين آخرين: Kandil, Yasser Ibrahim (Advisor), El-Tanani, Mohamed (Advisor)
التاريخ الميلادي: 2021
موقع: السلط
الصفحات: 1 - 71
رقم MD: 1210690
نوع المحتوى: رسائل جامعية
اللغة: الإنجليزية
الدرجة العلمية: رسالة ماجستير
الجامعة: جامعة عمان الأهلية
الكلية: عمادة الدراسات العليا والبحث العلمي
الدولة: الاردن
قواعد المعلومات: Dissertations
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المستخلص: Triple negative breast cancer is one of the most aggressive tumors with dismal survival and a high death rate due to lake of any target therapy. Overexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB-231 human breast cancer cells. The aim of this study was to investigate the potential of MELT-2017 as anticancer, targeted against the RAN gene, and to assess their effects in a range of biological assays. Methods The anticancer activity of MELT-2017 examined on MDA-MB-231 breast cancer cell line and A549 lung cancer cell line, using the [3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazolium bromide] MTT assay. Inhibition of the cell cycle and increased apoptosis were analysed by flowcytometry [propidium iodide (PI) and Annexin V staining], Also the anti-metastatic activity of MELT-2017 was investigated by using migration, invasion and colony formation assays. Finally, the expression levels of RAN GTP (RAN) gene were assessed using quantitative RT-PCR. Results MELT-2017 inhibited cell proliferation in MDA-MB-231 breast cancer cell line and A549 lung cancer cell line (IC50 10.6 μM for MDA-MB-231 and 25.3 μM for A549 cells), Annexin V assay verified that the cytotoxic effect of MELT-2017 was through apoptotic pathway on both cell lines. Furthermore, MELT-2017 also suppressed invasion and migration, and down regulated RAN GTPase in both cell line. Conclusion Current findings suggest that MELT-2017 may be potential therapeutic agents against TNBC.

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