Effects of shRNA-Mediated SOX9 Inhibition on Cell Proliferation and Apoptosis in Human HCC Cell Line Hep3B Mediated by Ultrasound-Targeted Microbubble Destruction (UTMD)

Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans. The survival rate of patients is still very poor as current therapies offer limited treatment efficacy. Therefore, it is necessary to explore novel and more effective strategies to treat HCC. Recently, Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a better alternative to viral vectors in delivering plasmid DNA into cells. In this study, we thus first determined the effect of combining UTMD with effectene on the transfection efficiency in human Hep3B cells. Transfection rate of the [effectene + shRNA-SOX9 + UTMD] group was the highest among the five groups, and were significantly higher than that of the [effectene + shRNA-SOX9] or [shRNA-SOX9 + UTMD] groups, while there was no significant difference between [shRNA-SOX9 alone] and [shRNA-SOX9 + UTMD] groups. Expression of SOX9 mRNA and protein was the lowest in effectene + shRNA-SOX9 + UTMD group. Moreover, transfection of shRNA-SOX9 with UTMD and effectene in combination could markedly inhibit the proliferation and induced cell apoptosis of Hep3B cells. These results suggest that the efficiency of gene delivery is remarkably increased when UTMD is combined with other transfection strategies, such as effectene. In conclusion, our research demonstrates that combining conventional transfection methods with UTMD achieves better transfection efficiency and that this can provide an improved gene delivery system for gene therapy.

SOX9 Is Essential for Triple-Negative Breast Cancer Cell Survival and Metastasis

“…Previous studies have also demonstrated the role of SOX9 in regulating cell apoptosis (39,40), however our results provide a novel mechanism by which the absence of SOX9 in TNBC cells, but not in SOX9-low non-TNBC cells, decreased cell survival. In additionally, SOX9 is also an important regulator of cell cycle.…”

Emodin inhibits proliferation and invasion, and induces apoptosis in human esophageal cancer cell line ECA109

“…Cytochrome c release facilitates formation of the apoptosome containing the adaptor Apaf-1 and the initiator caspase-9 in the presence of dATP, which in turn activates the downstream effector caspase-3 to induce cell apoptosis [13,14]. AIF can elicit cell apoptosis independent of caspase-3 activation [15]. The results obtained in this study showed enhanced expression of activated caspase-3 proteins, indicating that emodin triggered caspase-dependent apoptosis which is activated by the mitochondrial death pathway and/or the death receptor pathway.…”

VTIQ evaluates antitumor effects of NET‑1 siRNA by UTMD in HCC xenograft models

“…At present, liver carcinogenesis is considered to be stimulated by the accumulation of various genetic and epigenetic alterations ( 12 ). Compared with conventional treatment methods, including chemotherapy and surgery, gene therapy may kill tumor cells accurately and efficiently with fewer side effects ( 13 , 14 ).…”