Butorphanol affects the proliferation, migration and invasion of osteosarcoma MG-63 cells via Hippo/YAP signaling pathway / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨布托啡诺（BPH）对骨肉瘤（OS）细胞增殖、迁移和侵袭的影响及其相关的作用机制。方法：将MG-63细胞分为对照组、YAP抑制剂组（维替泊芬组）和BPH低、中、高浓度组，MTT法、克隆形成实验、FCM术、划痕愈合实验、Transwell实验、qPCR法、WB法和移植瘤实验分别检测处理后各组细胞的增殖活性、克隆形成数、细胞凋亡率、划痕愈合率，以及上皮钙黏蛋白（E-cadherin）、神经钙黏蛋白（N-cadherin）、波形蛋白（vimentin）mRNA的表达和YAP、TAZ蛋白的表达，同时观察BPH和维替泊芬对移植瘤生长的影响。结果：与对照组相比，维替泊芬组和BPH低、中、高浓度组细胞增殖活性、克隆数、划痕愈合率、侵袭细胞数，以及N-cadherin和vimentin mRNA水平、YAP和TAZ蛋白表达及移植瘤体积均显著降低（均P<0.05），细胞凋亡率、E-cadherin mRNA水平及对移植瘤的抑瘤率均升高（均P<0.05），且BPH高浓度组与维替泊芬组之间各项指标均无明显差异（均P>0.05）。结论：BPH可能通过抑制Hippo/YAP信号通路来抑制OS细胞MG-63增殖、迁移和侵袭。

In vitro skin retention and drug permeation study of Tongluo-Qutong rubber plaster by UPLC/UV/MS/MS

Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion