مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
4T1 derived exosomes enriched with miR-375 reduce 4T1 cells proliferation and induce apoptosis
4T1 derived exosomes enriched with miR-375 reduce 4T1 cells proliferation and induce apoptosis
Mahsa Hajivalili,1,*
1. Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
Introduction: Treatment of triple negative breast cancer (TNBC) is challenging due to lack of specific tumor antigens. Reduction of tumor suppressive microRNAs is a common phenomenon in different cancer types including TNBC. MiR-375 is a tumor suppressive miRNA with effective anti-cancer capability. Another player of the cancer progression is exosomes, small extracellular vesicles with biological functions, which are important in TNBC progression. In this regard we aimed to deliver miR-375 via tumor derived exosomes as a possible therapeutic approach.
Methods: The media of cultured 4T1 cells were collected and exosome enrichment conducted via exosome isolation kit. Then the extracted exosomes characterized through dynamic light scattering (DLS) and transmission electron microscopy (TEM). Loading of miR-375 conducted via modified Cacl2 method. The loading confirmed by Real-time PCR. For evaluation of proliferation, 4T1 cells were treated with different doses of 4T1 derived exosomes (Tex), 4T1 derived exosomes enriched with miR-375 (Tex-miR-375) (5, 25, 50, 100 μg/ml) and the proliferation rate evaluated by MTT test. Then 4T1cells treated with the specific doses analyzed for apoptosis via flow cytometry.
Results: Our results showed that Tex-miR375 effectively reduced the proliferation rate of 4T1 cells after 48 hour in a dose dependent manner (25 μg/ml). In parallel, an induction in apoptosis detected after 24 hours in 4T1 cells treated with Tex-miR-375 compared to Tex and untreated cells.
Conclusion: In conclusion, TEX-miR375 can be considered as a promising therapeutic approach for TNBC
Keywords: Breast cancer, mi RNA, extra cellular vesicles, MTT