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

Abstract

Ultrasound-targeted microbubble destruction (UTMD) has recently been developed as a promising noninvasive tool for organ-and tissue-specific gene or drug delivery. The aim of the present study was to explore the role of UTMD-mediated Sirtuin 3 (SIRT3) overexpression in the malignant behaviors of human ovarian cancer (HOC) cells. Reverse transcription-quantitative PCR was performed to detect SIRT3 mRNA expression levels in normal human ovarian epithelial cells and HOC cell lines; low SIRT3 expression was found in HOC cell lines, and the SKOV3 cell line was used in the following experiments. The SIRT3-microbubble (MB) was prepared, and the effects of ultrasound-treated SIRT3-MB on biological processes of SKOV3 cells were determined. The proliferation, migration, invasion and apoptosis of SKOV3 cells were measured after SIRT3 upregulation by UTMD. Xenograft tumors in nude mice were induced to observe tumor growth in vivo. Upregulation of SIRT3 inhibited the malignant behaviors of SKOV3 cells, whereas UTMD-mediated SIRT3 upregulation further inhibited proliferation, epithelial-mesenchymal transition, invasion and migration, and induced apoptosis of SKOV3 cells, and it also inhibited tumor formation and growth in vivo. Moreover, the present study identified hypoxia inducible factor-1α (HIF-1α) as a target of SIRT3. The present study provided evidence that UTMD-mediated overexpression of SIRT3 may suppress HOC progression through the inhibition of HIF-1α.

Ultrasound-Targeted Microbubble Destruction-Mediated Inhibition of Livin Expression Accelerates Ovarian Cancer Cell Apoptosis

“…It was suggested that ultrasound-targeted microbubble destruction contributed to effective inhibition of Livin in ovarian cancer cells, resulting in accelerating cell apoptosis and reducing cell survival rate. These findings were similar to another study, indicating that overexpression of sirtuin-3 mediated by targeted microbubble destruction was helpful to inhibit the progression of ovarian cancer [ 32 ]. The research presented by Chen et al pointed out that ultrasound microbubble destruction targeting survivin induced apoptosis of HeLa cells in cervical cancer and led to inhibit the progression of cervical cancer [ 33 ].…”

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies

“…Sirts are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target a variety of protein substrates that has effects on oxidative stress regulation, metabolism, cell survival, division, and aging ( 124 , 125 ). Among the sirtuins, Sirt3, a genomically expressed, mitochondrial-located tumor suppressor protein has an aberrantly low level of expression in various cancers including OCs ( 126 – 128 ) where Sirt3 has anti-proliferative and anti-migratory effects. Sirt3 gene delivery by UTMD in vitro inhibited proliferation, epithelial-to-mesenchymal transition, and migration, and induced apoptosis and cell cycle arrest of SKOV3 cells.…”

“…Sirt3 gene delivery by UTMD in vitro inhibited proliferation, epithelial-to-mesenchymal transition, and migration, and induced apoptosis and cell cycle arrest of SKOV3 cells. Furthermore, UTMD delivery of Sirt3 in mice bearing SKOV3 xenograft tumor suppressed tumor volume and weight with an attendant decrease in Ki67 positive cells ( 126 ).…”