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

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.