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。

Objective: To investigate the impacts of butorphanol (BPH) on the proliferation, migration and invasion of osteosarcoma (OS) cells and the relevant mechanism. Methods: MG-63 cells were grouped into a control group, a YAP inhibitor group (Verteporfin group), and low, medium and high concentration BPH groups. The cytotoxicity and proliferative activity of each group of cells were detected by MTT, the number of cell clones was detected by clonogenic assay, the apoptosis of cells was detected by flow cytometry, the migration ability of the cells was detected by wound-healing test, and the invasion ability of the cells was detected by Transwell assay. The mRNA expression of E-cadherin, N-cadherin and vimentin was detected by qPCR, and the protein expression of YAP and TAZ was detected by WB assay. Besides, the effects of BPH and verteporfin on growth of transplanted tumors were also observed. Results: Compared with the control group, the cell proliferation activity, the number of clones, the rate of wound healing, the number of invaded cells, the mRNA levels of N-cadherin and vimentin, the protein expression of YAP and TAZ, and the tumor volumes were obviously lower (all P<0.05), while the apoptosis rate, mRNA level of E-cadherin and the transplanted tumor inhibition rate were significantly higher (all P<0.05) in the Verteporfin group and the low, medium and high concentration BPH groups.There were no obvious differences in above observation indices between the high concentration BPH and the Verteporfin group (P>0.05). Conclusion: BPH may inhibit the proliferation, migration and invasion of OS cells by inhibiting Hippo/YAP signaling pathway.

徐州医科大学附属医院基金项目（No. XYFM2020046）