咪达唑仑调节YAP/TAZ信号通路对骨肉瘤细胞增殖凋亡和侵袭的影响

doi:10.3969/j.issn.1006-6233.2024.01.01

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Abstract Objective: To investigate the effects of midazolam (MDZ) on the proliferation, apoptosis and invasion of osteosarcoma (OS) cells by regulating the Yes associated protein (YAP)/PDZ transcriptional activator of transcription (TAZ) signaling pathway. Methods: qRT-PCR and western blot were applied to detect the expression of YAP, TAZ mRNA, and proteins in normal osteoblast and OS cell lines, and to screen the optimal intervention cell line. OS cells were intervened with different concentrations of MDZ (0, 12.5, 25, 50, 100, 200 μmoL/L), MTT method was applied to detect cell proliferation activity and screen the optimal intervention concentration; OS cells were randomly divided into control group, MDZ group, pcDNA3.1 group, and pcDNA3.1-YAP/TAZ group, and transfection efficiency was detected using qRT-PCR method; EdU staining, flow cytometry, and Transwell cells were applied to detect cell proliferation, apoptosis, and invasion, respectively; Western blot method was applied to detect the expression of proliferating cell nuclear antigen (PCNA), Bcl-2 associated X protein (Bax), N-cadherin, E-cadherin, and YAP, TAZ proteins; OS nude mouse model was constructed, and grouped into a control group and an MDZ group, immunohistochemical methods were applied to detect the expression of Ki-67, YAP, and TAZ proteins in transplanted tumor tissue, and TUNEL staining was applied to detect apoptosis. Results: The expression levels of YAP and TAZ mRNA and protein in OS cell lines were obviously increased (P<0.05); MDZ obviously reduced the expression of PCNA, N-cadherin, YAP, and TAZ, inhibitd the proliferation and invasion of MG63 and U20S cells, increased the expression of Bax and E-cadherin, and promoted cell apoptosis. Overexpression of YAP/TAZ was able to reverse the inhibitory effects of MDZ on the proliferation and invasion of MG63 and U20S cells, and promote the apoptosis of MG63 and U20S cells (P<0.05); in vivo experiments showed that MDZ obviously reduced the mass and volume of transplanted tumors, and the expression levels of Ki-67, YAP, and TAZ, promoted apoptosis of transplanted tumor cells (P<0.05). Conclusion: MDZ may inhibit the YAP/TAZ signaling pathway, inhibit the proliferation and invasion of OS cells, and promote apoptosis.

Key words： Midazolam YAP/TAZ Osteosarcoma Proliferation Apoptosis Invasion

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	AO Tingting
	TU Mengjia
	ZHANG Xi

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AO Tingting,TU Mengjia,ZHANG Xi. Effects of Midazolam on Proliferation Apoptosis and Invasion of Osteosarcoma Cells by Regulating the YAP/TAZ Signaling Pathway[J]. HeBei Med, 2024, 30(1): 1-8.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.01.01 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I1/1

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