香叶木素通过调节Hippo通路对胰腺癌细胞增殖迁移和侵袭及上皮间质转化的影响

doi:10.3969/j.issn.1006-6233.2025.03.03

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Abstract Objective: To investigate the effects of diosmetin (DIO) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Hippo pathway. Methods: Human pancreatic cancer cells (PANC-1) were treated with diosmetin at concentrations ranging from 0.625μg/mL to 20 μg/mL to determine the optimal experimental concentration. PANC-1 cells were divided into the following groups: Control group, low-concentration diosmetin group (D-L), medium-concentration diosmetin group (D-M), high-concentration diosmetin group (D-H), and YAP inhibitor verteporfin group (VP). Except for the Control group, cells in the other groups were treated with the corresponding drugs. The effects of diosmetin on PANC-1 cell proliferation, migration, and invasion were assessed. Protein expression was detected by Western blotting, and the impact of diosmetin on pancreatic cancer xenograft growth was evaluated in a mouse model. Results: Diosmetin concentrations of 2.5μg/mL, 5.0μg/mL, and 10.0μg/mL were selected for subsequent experiments. Compared to the Control group, the D-L, D-M, and D-H groups showed reduced Edu-positive rates, scratch healing rates, and cell invasion numbers, along with downregulated expression of PCNA, MMP-2, MMP-9, N-cadherin, and vimentin, and upregulated expression of E-cadherin, p-YAP/YAP, and p-TAZ/TAZ (P<0.05). Compared to the D-H group, the VP group exhibited increased Edu-positive rates, scratch healing rates, and cell invasion numbers, upregulated expression of PCNA, MMP-2, MMP-9, N-cadherin, and vimentin, and downregulated expression of E-cadherin, p-YAP/YAP, and p-TAZ/TAZ (P<0.05). In the mouse xenograft model, the diosmetin group showed reduced tumor volume and weight, along with upregulated expression of p-YAP/YAP and p-TAZ/TAZ (P<0.05). Conclusion: Diosmetin inhibits the proliferation, migration, invasion, and EMT of pancreatic cancer cells by activating the Hippo pathway.

Key words： Diosmetin Pancreatic cancer Hippo pathway Proliferation Migration Invasion Epithelial-mesenchymal transition

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.03.03 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I3/368

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