Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.
To analyze and summarize the experience of single-port robotic-assisted single-port laparoscopic ambulatory surgery (AS) for intraligamental myomectomy. Analyzed the basic conditions, preoperative myoma assessment, surgical operation, and perioperative management of two patients undergoing robotic-assisted laparoendoscopic single site (R-LESS) intraligamental myomectomy and reviewed in the literature to summarize the initial clinical experience of the robotic AS model. Two cases of R-LESS intraligamental myomectomy were successfully discharged after 29.82 h and 25.95 h of hospitalization, respectively, with no complications. R-LESS intraligamental myomectomy to achieve AS is safe and feasible. Adequate preoperative myoma evaluation, staging and strict access criteria, combined with current advanced single-port robotic technology and meticulous intraoperative management, and a scientific perioperative Enhanced Recovery After Surgery (ERAS) management process are the keys to enable AS for intraligamental myomectomy.
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