Ultrasound microbubbles mediated miR-let-7b delivery into CD133+ ovarian cancer stem cells

Abstract

Ovarian cancer stem cells (OCSCs) are considered the reason for ovarian cancer’s emergence and recurrence. Ultrasound-targetted microbubble destruction (UTMD), a non-vial, safe, and promising delivery method for miRNA, is reported to transfect cancer stem cells (CSCs). In the present study, we investigated to transfect miR-let-7b into OCSCs using UTMD. The CD133+ OCSCs, accounted for only 0.1% of ovarian cancer cell line A2780, were separated by flow cytometry, and the CSC characteristics of CD133+ OCSCs have been proved by spheroid formation and self-renewal assay. The miR-let-7b transfection efficiency using UTMD was significantly higher than other groups except lipofectamine group through flow cytometry. The cell viability of all groups decreased after transfection, and the late apoptosis rate of CD133+ OCSCs after miR-let7b transfection induced by UTMD was 2.62%, while that of non-treated cells was 0.02% (P<0.05). Furthermore, the Western blot results demonstrated that the stem cells surface marker of CD133 expression has decreased. Therefore, our results indicated that UTMD-mediated miRNA delivery could be a promising platform for CSC therapy.

<p>The better effects of microbubble ultrasound transfection of miR-940 on cell proliferation inhibition and apoptosis promotion in human cervical cancer cells</p>

“…Microbubble ultrasound contrast agent-mediated gene transfection would be an advantageous transfection method to be widely used in the future. Ultrasound microbubble-mediated miRNA delivery into CD133+ ovarian cancer stem cells and human hepatoma HepG2 cells have been reported, and the effects were found better than the single liposome, microbubble or ultrasound,18,34 which were consistent with our research.…”

Inhibition of microRNA let‐7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer

“…Studies have shown that let‐7b inhibition increases the expression of HMGA2, 17 c‐Myc, Dicer, and Imp3 10 in ovarian cancer cells. Another study introduced let‐7b into ovarian cancer stem cells with ultrasound microbubbles, which resulted in significantly increased cell apoptosis and a decrease in the expression of CD133, a cancer stemness marker 18 . However, it is unknown whether CD133 is the direct target of let‐7b.…”

Ultrasound‑targeted microbubble destruction enhances the anti‑tumor action of miR‑4284 inhibitor in non‑small cell lung cancer cells

“…For instance, UTMD technology is able to significantly facilitate the co-transmission of gemcitabine and miR-21i and thus provides a promising strategy for the effective treatment of pancreatic cancer ( 33 ). In the study of Yang et al ( 34 ), miR-let-7b was transfected into ovarian cancer stem cells by flow cytometry, and the results indicated that miR-let-7b transfection efficiency using UTMD was significantly higher. In NSCLC, the expression level of miR-767 could be successfully downregulated by miR-767 inhibitor and UTMD further enhanced the transfection efficacy of miR-767 inhibitor, while downregulation of miR-767 was indicated to inhibit the proliferation, migration and invasion of tumor cells ( 15 ).…”