Context: Limonoids possess broad range of biological activities, including antitumour, antimicrobial and antioxidant activities, etc. Eudesmin (EDN) is a type of limonoid which also possesses various activities. However, there is no report on the antitumour lung cancer (LC) activities of this compound.Objective: The present study investigates the antitumour effects of EDN and its potential molecular mechanisms.Materials and methods: The in vitro antitumour effects of EDN on LC A549 cells were evaluated by using MTT assay. The in vivo antitumour effects were investigated on a xenograft athymic nude mouse model. The mice were administered orally with EDN (10, 20 and 40 mg/kg) once daily for 28 days. Effects of EDN on apoptosis-related or signalling proteins (Bcl-2, Bax, caspase-3, caspase-9, P53, Akt and JNK) were assayed by western blot analysis.Results: EDN showed significant inhibitory effects on the growth of LC A549 cells in vitro with the half maximal inhibitory concentration (IC50) of 18.3 μM. By treating with EDN (10, 20 and 40 μM), expression of caspase-3, caspase-9, Bax, P53 and phosphorylated JNK in A549 cells were significantly upregulated, whereas expression of Bcl-2 and Akt phosphorylation were significantly down-regulated. Interestingly, EDN-induced apoptosis could be attenuated by JNK inhibitor. In addition, in vivo experiments also indicated EDN (10, 20 and 40 mg/kg) had significant antitumour effects (p < 0.01) on nude mice.Conclusions:Overall, the results indicated that EDN possesses significant antitumour effects on LC and the possible mechanism might be related to induction of mitochondria-mediated apoptosis.
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.
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