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首页|期刊导航|中国肿瘤生物治疗杂志|茯苓酸通过调控AKT/MDM2/p53通路影响结直肠癌HCT116细胞的恶性生物学行为

茯苓酸通过调控AKT/MDM2/p53通路影响结直肠癌HCT116细胞的恶性生物学行为OA北大核心CSTPCD

Pachymic acid affects the malignant biological behaviors of colorectal cancer HCT116 cells by modulating the AKT/MDM2/p53 pathway

中文摘要英文摘要

目的:探究茯苓酸(PA)是否通过AKT/MDM2/p53通路影响结直肠癌HCT116细胞的恶性生物学行为.方法:常规培养HCT116细胞,并将其分为对照组、MK-2206(AKT抑制剂)组、PA低浓度(PA-L)组、PA高浓度(PA-H)组、PA-H+ SC79(AKT激活剂)组.CCK-8法、细胞克隆形成实验、流式细胞术、Transwell、qPCR法和WB法实验分别检测各组HCT116细胞的增殖活力,克隆形成能力,细胞凋亡,迁移、侵袭能力,E-cadherin、N-cadherin和vimentin mRNA表达以及AKT/MDM2/p53通路相关蛋白的表达.结果:PA可明显抑制HCT116细胞的增殖活力(P<0.05)、克隆形成能力(P<0.05)、迁移和侵袭能力(P<0.05),诱导其凋亡(P<0.05),抑制N-cadherin、vimentin mRNA的表达(P<0.05),促进E-cadherin mRNA的表达(P<0.05),抑制AKT、MDM2的磷酸化水平(P<0.05),促进p53蛋白的表达(P<0.05);AKT抑制剂MK-2206可模拟PA的作用(均P<0.05),而其激活剂SC79则可逆转PA的作用(均P<0.05).结论:PA通过调控AKT/MDM2/p53信号通路来抑制HCT116细胞的增殖、迁移和侵袭并诱导其凋亡.

Objective:To investigate whether pachymic acid(PA)affects the malignant biological behaviors of colorectal cancer(CRC)HCT116 cells through the AKT/MDM2/p53 pathway.Methods:HCT116 cells were routinely cultured and divided into control group,MK-2206(AKT inhibitor)group,low PA concentration(PA-L)group,high PA concentration(PA-H)group,and PA-H+SC79(AKT activator)group.CCK-8,Cell clone formation assay,flow cytometry and Transwell assay were used to detect the proliferation viability,clone formation ability,apoptosis,migration and invasion of HCT116 cells in each group.qPCR was used to determine the mRNA expression of E-cadherin,N-cadherin and vimentin,and WB assay was applied to detect the expression of AKT/MDM2/p53 pathway related proteins.Results:PA significantly suppressed the proliferation(P<0.05),clone formation ability,migration and invasion and induced apoptosis(all P<0.05)of HCT116 cells,inhibited the mRNA expression of N-cadherin and vimentin while promoted the mRNA expression of E-cadherin(all P<0.05),decreased the phosphorylation levels of AKT and MDM2(both P<0.05),and elevated the protein expression of p53(P<0.05)in HCT116 cells.The AKT inhibitor MK-2206 could mimic the effects of PA(all P<0.05),while its activator SC79 could reverse the effects of PA(all P<0.05).Conclusion:PA inhibits proliferation,migration and invasion and induces apoptosis of HCT116 cells by regulating the AKT/MDM2/p53 signaling pathway.

张美华;赵文睫;李康;曲巧燕;郝建波

青岛大学附属青岛市中心医院 内镜中心,山东 青岛 266000青岛大学附属青岛市中心医院 内镜中心,山东 青岛 266000||青岛市立医院消化内科,山东 青岛 266000青岛大学附属青岛市中心医院 结直肠肛门外科,山东 青岛 266000

临床医学

茯苓酸结直肠癌AKT/MDM2/p53通路增殖迁移侵袭凋亡

pachymic acid(PA)colorectal cancerAKT/MDM2/p53 pathwayproliferationmigrationinvasionapoptosis

《中国肿瘤生物治疗杂志》 2024 (003)

247-252 / 6

青岛市医药卫生科研指导项目(No.2022-WJZD063)

10.3872/j.issn.1007-385x.2024.03.006

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