Ultrasound-Targeted Microbubble Destruction (UTMD) Combined with Liposome Increases the Effectiveness of Suppressing Proliferation, Migration, Invasion, and Epithelial- Mesenchymal Transition (EMT) via Targeting Metadherin (MTDH) by ShRNA

Abstract

Background Reports show that ultrasound-targeted microbubble destruction (UTMD) is a promising method of gene therapy, and metadherin (MTDH) is related to the development of breast cancer. Thus, we investigated the role of MTDH in breast cancer and compared the effect of suppressing MTDH by shRNA using liposome, UTMD, or the combination of these 2 methods. Material/Methods Graphing of survival curves of MTDH was analyzed by bioinformatics. UTMD was conducted using an ultrasonic therapeutic apparatus. Cell counting kit-8 (CCK-8) assay was used to measure cell viability. Migration and invasion rates were measured by wound healing test and Transwell invasion assay, respectively. The expression of MTDH, E-cadherin, metastasis-associated protein-1 (MTA-1), matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot and qPCR. Results The prognosis of breast cancer can be decreased by the high expression of MTDH, and elevated expression of MTDH was discovered in MCF-7, MCF-10A, and T47D cell lines. UTMD combined with liposome is most efficient in transfecting shRNA, clearly suppressing the expression of MTDH and thereby decreasing cell viability, migration, invasion rate, and epithelial- mesenchymal transition (EMT) processes in the MCF-7 cell line. Conclusions UTMD combined with liposome could be used as a more efficient way to transfect shRNA into cells to suppress the expression of MTDH and thus lead to the downregulation of proliferation, migration, and EMT processes of the MCF-7 cell line, showing the potential for use in gene therapy.

Ultrasound‑targeted microbubble destruction‑mediated overexpression of Sirtuin 3 inhibits the progression of ovarian cancer

“…UTMD has emerged rapidly in recent years as a novel technique for gene therapy that shows potential for wide use in gene therapy and cell biology. For instance, UTMD combined with liposomes has been suggested to promote short hairpin (sh)RNA transfection efficiency into cells to inhibit metadherin expression, thus leading to the downregulation of proliferation and metastatic processes in MCF-7 breast cancer cells ( 35 ). Similarly, UTMD-mediated HIF-1 shRNA transfection has served an enhancing role in tumor growth inhibition ( 36 ).…”

Nanoliposomes as nonviral vectors in cancer gene therapy

“… 163 Furthermore, ultrasound‐targeted microbubble destruction significantly enhances the potential of shRNA‐loaded liposomes in cancer suppression. 164 Overall, all these studies support the use of liposomes as carriers for shRNA delivery and cancer treatment. Various genes like Hsp70, eIF3i, and WT1 have been targeted by shRNA‐loaded liposomes and more studies are required to target additional molecular pathways responsible for cancer progression.…”

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy

“…119 Therefore, nanoparticles have opened a new window for treatment of breast cancer via shRNA delivery. 120…”

“…Nanocarriers had particle sizes of 12 and 50 nm and a zeta potential of 48.7 mV, showing their high stability (Figure 3). 119 Therefore, nanoparticles have opened a new window for treatment of breast cancer via shRNA delivery 120 …”