羟基红花黄色素A通过Hippo途径调控糖酵解影响结直肠癌细胞增殖侵袭和凋亡

doi:10.3969/j.issn.1006-6233.2025.07.01

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摘要 目的: 探讨羟基红花黄色素A(HSYA)对结直肠癌HT29细胞增殖和侵袭的影响及其作用机制。方法: 将HT29细胞分为5组:Con组(HT29细胞)、HSYA低剂量组(HSYA-L组,HT29+20μmoL/L HSYA)、HSYA中剂量组(HSYA-M组,HT29+30μmoL/L HSYA)、HSYA高剂量组(HSYA-H组,HT29+40μmoL/L HSYA)和XMU-MP-1(Hippo抑制剂XMU-MP-1,HT29+40μmoL/L HSYA+3μmoL/L XMU-MP-1)。采用CCK-8实验检测HSYA对HT29细胞增殖活性的影响并计算半抑制浓度(IC₅₀)值;采用EdU增殖实验、细胞划痕实验和Transwell实验检测HT29细胞增殖、迁移和侵袭能力;流式细胞术检测细胞凋亡率;相应试剂盒检测HT29细胞中葡萄糖消耗量、乳酸生成量;采用Western Blot方法检测糖酵解和Hippo途径相关蛋白表达水平。结果: 与Con组相比,HSYA-L组、HSYA-M组、HSYA-H组细胞活力、增殖率、迁移率和穿膜细胞数、葡萄糖消耗量、乳酸生成量、HXK2、LDHA显著降低(P<0.05),凋亡率、p-MST1/2、p-LATS1/2、YAP、TAZ水平显著升高(P<0.05),且呈剂量依赖性;与XMU-MP-1组相比,HSYA-H组细胞活力、增殖率、迁移率和穿膜细胞数、葡萄糖消耗量、乳酸生成量、HXK2、LDHA显著降低(P<0.05),凋亡率、p-MST1/2、p-LATS1/2、YAP、TAZ水平显著升高(P<0.05)。结论: HSYA能够显著抑制HT29细胞的增殖、迁移和侵袭,并诱导细胞凋亡,其机制可能与激活Hippo途径,进而调控糖酵解过程相关。

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	周矗
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关键词 ：羟基红花黄色素A, Hippo途径, 结直肠癌, 细胞增殖, 细胞侵袭

Abstract：Objective: To investigate the effect of hydroxysafflor yellow A(HSYA) on the proliferation invasion and apoptosis of colorectal cancer HT29 cells and its mechanism. Methods: HT29 cells were divided into 5 groups: Con group (HT29 cells), HSYA low dose group (HSYA-L group, HT29+20 μmoL/L HSYA), HSYA medium dose group (HSYA-M group, HT29+ 20 μmoL/L HSYA), HSYA high dose group (HSYA-H group, HT29+20 μmoL/L HSYA), HSYA high dose group (HSYA-H group, HT29+30 μmoL/L HSYA) HT29+40 μmoL/L HSYA) and XMU-MP-1 group (Hippo inhibitor XMU-MP-1, HT29+40 μmoL/L HSYA+3 μmoL/L XMU-MP-1). The effect of HSYA on the proliferative activity of HT29 cells was detected by CCK-8 and the half-inhibitory concentration (IC₅₀) was calculated. The proliferation, migration and invasion ability of HT29 cells were detected by EdU proliferation assay, cell scratch assay and Transwell assay. The apoptosis rate was detected by flow cytometry. Glucose consumption and lactic acid production in HT29 cells were detected by corresponding kits. The expression levels of glycolysis and Hippo pathway related proteins were detected by Western Blot. Results: Compared with Con group, cell viability, proliferation rate, mobility, number of transmembrane cells, glucose consumption, lactic acid production, HXK2 and LDHA in HSYA-L, HSYA-M and HSYA-H groups were significantly decreased (P<0.05). The apoptosis rate, p-MST1/2, p-LATS1/2, YAP and TAZ levels were significantly increased (P<0.05) in a dose-dependent manner. Compared with XMU-MP-1 group, cell viability, proliferation rate, mobility, number of transmembrane cells, glucose consumption, lactic acid production, HXK2 and LDHA in HSYA-H group were significantly decreased (P<0.05), while apoptosis rate, p-MST1/2, p-LATS1/2, YAP and TAZ levels were significantly increased (P<0.05). Conclusion: HSYA can significantly inhibit the proliferation, migration and invasion of HT29 cells and induce cell apoptosis, which may be related to the activation of Hippo pathway and the regulation of glycolysis process.

Key words： Hydroxysafflor yellow A Hippo pathway Glycolysis Colorectal cancer Cell proliferation Cell invasion

基金资助:2021年四川省医学(青年创新)科研项目,(编号:S21129)

通讯作者: 王云

引用本文:

周矗, 周瑀, 安玲, 王云. 羟基红花黄色素A通过Hippo途径调控糖酵解影响结直肠癌细胞增殖侵袭和凋亡[J]. 河北医学, 2025, 31(7): 1057-1063.
ZHOU Chu, ZHOU Yu, AN Ling, et al. Hydroxylsafflower Yellow A Affecting the Proliferation Invasion and Apoptosis of Colorectal Cancer Cells by Regulating Glycolysis through Hippo Pathway. HeBei Med, 2025, 31(7): 1057-1063.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.07.01 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I7/1057

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