原苏木素A调节AMPK/ACC信号通路对乳腺癌细胞增殖、凋亡和放射敏感性的影响OA
Impacts of protosappanin A on proliferation,apoptosis and radiosensitivity of breast cancer cells by modulating the AMPK/ACC signaling pathway
目的:探究原苏木素A(PrA)调节AMP活化蛋白激酶(AMPK)/乙酰辅酶A羧化酶(ACC)信号通路对乳腺癌细胞增殖、凋亡和放射敏感性的影响.方法:体外培养乳腺癌细胞(MCF-7),分为对照组(正常培养)、L-PrA组、M-PrA组、H-PrA组(分别用400、800、1600 μmol/L的PrA处理)、Compound C组(1 600 μmol/L的PrA和1 μmol/L AMPK/ACC信号通路抑制剂Compound C处理).CCK-8筛选合适的PrA浓度及检测各组细胞的增殖;集落形成实验检测各组细胞的放射敏感性;划痕和Transwell实验测定细胞的迁移和侵袭;流式细胞术检测各组细胞凋亡;免疫印迹检测细胞增殖、迁移侵袭、凋亡、AMPK/ACC信号通路相关蛋白的表达.结果:不同剂量PrA处理组与对照组相比,细胞存活分数(SF)、增殖率、迁移率、侵袭数、增殖细胞核抗原(PCNA)、基质金属蛋白酶(MMP)-2、MMP-9、Bcl-2表达减少,放射增敏比(SER)、细胞凋亡率、Bax、cleaved caspase-3、磷酸化AMPK(p-AMPK)/AMPK、磷酸化ACC(p-ACC)/ACC表达增加;Compound C组与H-PrA组相比,细胞SF、增殖率、迁移率、侵袭数、PCNA、MMP-2、MMP-9、Bcl-2表达显著增加,细胞的SER、细胞凋亡率、Bax、cleaved caspase-3、p-AMPK/AMPK、p-ACC/ACC表达显著减少.结论:PrA可能通过激活AMPK/ACC信号通路,抑制乳腺癌细胞增殖、迁移侵袭,促进细胞凋亡和增强放射敏感性.
Objective:To explore the impacts of protosappanin A(PrA)on the proliferation,apoptosis and radiosensitivity of breast cancer cells by modulating the AMP-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling pathway.Methods:Breast cancer cells(MCF-7)were cultured in vitro and randomly divided into control group(normal culture),L-PrA group,M-PrA group,H-PrA group(treated with 400,800,1 600 μmol/L PrA),and Compound C group(treated with 1 600 μmol/L PrA and 1 μmol/L Compound C,an AMPK/ACC pathway inhibitor).Cell proliferation was assessed by CCK-8 assay to select appropriate PrA concentrations and to compare proliferative activity across groups.The colony formation experiment was performed to detect cell radiosensitivity.Scratch wound-healing and Transwell assays were adopted to measure cell migration and invasion.Flow cytometry was utilized to assess the apoptosis of cells in each group.Western blotting was employed to analyze the proteins associated with proliferation,migration,invasion,apoptosis,and the AMPK/ACC signaling pathway in cells.Results:Compared with the control group,PrA treatment groups showed dose-dependent decreases in cell survival fraction(SF),proliferation rate,migration rate,invasion number,and expression of PCNA,MMP-2,MMP-9,and Bcl-2,and increases in sensitization enhancement ratio(SER),apoptosis rate,and expression of Bax,cleaved caspase-3,p-AMPK/AMPK,and p-ACC/ACC.Compared with the H-PrA group,the Compound C group exhibited significant rises in SF,proliferation rate,migration rate,invasion number,and expression of PCNA,MMP-2,MMP-9,and Bcl-2,while demonstrating decreases in SER,apoptosis rate,and expression of Bax,cleaved caspase-3,p-AMPK/AMPK,and p-ACC/ACC.Conclusion:PrA may activate the AMPK/ACC signaling pathway,thereby inhibiting breast cancer cell proliferation,migration and invasion,promoting cell apoptosis,and enhancing radiosensitivity.
郭帅;徐雪峰;吴建亭
南通市肿瘤医院放疗科,南通 226361南通市肿瘤医院放疗科,南通 226361南通市肿瘤医院放疗科,南通 226361
医药卫生
乳腺癌原苏木素AAMP活化蛋白激酶乙酰辅酶A羧化酶增殖凋亡放射敏感性
breast cancerprotosappanin AAMP-activated protein kinaseacetyl-CoA carboxylaseproliferationapoptosisradiosensitivity
《解剖学杂志》 2026 (1)
41-46,84,7
南通市卫生健康委员会科研(MSZ2023033)
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