RÉSUMÉ
Background: Although there are many treatments for breast cancer, such as surgery, radiotherapy, chemotherapy, estrogen receptor antagonists, immune checkpoint inhibitors and so on. However, safer and more effective therapeutic drugs for breast cancer are needed. Sinensetin, a safer therapeutic drugs, come from citrus species and medicinal plants used in traditional medicine, while its role and underlying mechanism in breast cancer remain unclear. Our study aimed to investigate the role and mechanism of sinensetin in breast cancer. Methods: Cell Counting Kit-8 (CCK-8) was used to determine the safe concentration of sinensetin in MCF-10A, MCF7 and MDA-MB-231 cells; 120 µM sinensetin was used in subsequent experiments. Real time polymerase chain reaction (RT-PCR), Western blotting, Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay, Transwell invasion assay and Clone formation assay were used in this study to determine cell viability, mRNA expression, protein levels, apoptosis, proliferation, invasion and so on. Results: Herein, our results showed that 120 µM sinensetin suppressed the cell viability and promoted apoptosis of MCF7 and MDA-MB-231 cells. Treatment with 120 µM sinensetin for 24 h showed no significant toxicity to normal mammary cells; 120 µM sinensetin decreased cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), and downregulated ß-catenin, lymphatic enhancing factor 1 (LEF1), T-cell factor (TCF) 1/TCF7, and TCF3/TCF7L1 expression in MCF7 and MDA-MB-231 cells. The Wnt agonist SKL2001 reversed the inhibitory effect of sinensetin on cell survival, metastasis, and EMT. Sinensetin-induced downregulation of ß-catenin, LEF1, and TCF1/TCF7 expression were upregulated by SKL2001 in MCF7 and MDA-MB-231 cells. Conclusions: In summary, sinensetin suppressed the metastasis of breast cancer cell via inhibition of Wnt/ß-catenin pathway and there were no adverse effects on normal breast cells. Our study confirmed the role of sinensetin in breast cancer cells and provided a better understanding of the underlying mechanism.
RÉSUMÉ
OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial chemoembolization combined with percutaneous ethanol injection in treating unresectable primary liver cancer. METHODS: MEDLINE (1966-June 2008), EMBASE (1974-June 2008), the Cochrane Library (Issue 2, 2008), CBMdisc (1978-June 2008), CNKI (1979-June 2008), and Wanfang Database were searched without language limitation. All randomized controlled trials comparing transcatheter arterial chemoembolization alone with transcatheter arterial chemoembolization combined with percutaneous ethanol injection for treating unresectable primary liver cancer were identified and screened by two reviewers, and the methodological quality of the included randomized controlled trials were evaluated by Jadad scale. The Cochrane Collaboration's RevMan4.2 software was used for the analysis of the data extracted from the included randomized controlled trials. RESULTS: Fourteen randomized controlled trials involving 857 patients were included with 12 trials published in Chinese and 2 in English. Meta-analysis of the data extracted from the included randomized controlled trials showed that transcatheter arterial chemoembolization combined with percutaneous ethanol injection could significantly improve the overall survival rates compared with transcatheter arterial chemoembolization alone, with the corresponding relative risk (RR) values (95% CI) for the 1, 2, and 3-year survival of 1.37 (1.21 - 1.56), 1.74 (1.49 - 2.04), and 2.26 (1.70 - 3.02) respectively; and the RR alpha-feto-protein (AFP) negative conversion rate, AFP lowering rate, and tumor focus efficacy rate were 1.39 (1.24 - 1.56), 1.69 (1.38 - 2.07), and 1.56 (1.38 - 1.77) respectively. Side effects or adverse events related with transcatheter arterial chemoembolization were reported in 11 randomized controlled trials, mainly liver function impairment, fever, gastrointestinal symptom, and transient pain, and no major treatment-related complication or death was reported. CONCLUSION: Compared with transcatheter arterial chemoembolization alone, transcatheter arterial chemoembolization combined with percutaneous ethanol injection significantly is a better approach in treating unresectable primary liver cancer, increasing the overall survival rate, AFP negative and lowering rates, and tumor response rate. However, the methodological quality of most reported randomized controlled trials is low.
