SIRT3通过AKT信号通路调节食管鳞状细胞癌对顺铂的敏感性

doi:10.3760/cma.j.cn441417-20250327-18013

国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (18): 3058-3064.DOI: 10.3760/cma.j.cn441417-20250327-18013

SIRT3通过AKT信号通路调节食管鳞状细胞癌对顺铂的敏感性

袁明亮¹ 陆羽² 叶欣¹ 杨希¹ 余学春¹

¹南京医科大学康达学院附属盱眙人民医院消化内科，淮安 211700；²南京医科大学康达学院附属盱眙人民医院临床研究中心，淮安 211700

收稿日期:2024-03-27 出版日期:2025-09-15 发布日期:2025-09-26
通讯作者: 余学春，Email： xuechunyu2009@sina.com
基金资助:
国家中医药管理局胃癌毒邪论治重点研究室开放课题（202261）；江苏省卫生健康委员会项目（Z2021035）；淮安市自然科学研究计划（HABZ202215）；淮安市卫生健康委员会科学基金资助项目（HAWJ202032）

SIRT3 regulates the sensitivity of esophageal squamous cell carcinoma to cisplatin through the AKT signaling pathway

Yuan Mingliang¹, Lu Yu², Ye Xin¹, Yang Xi¹, Yu Xuechun¹

¹Department of Gastroenterology, Affiliated Xuyi People's Hospital of Kangda College, Nanjing Medical University, Huai'an 211700, China; ²Clinical Research Center, Affiliated Xuyi People's Hospital of Kangda College, Nanjing Medical University, Huai'an 211700, China

Received:2024-03-27 Online:2025-09-15 Published:2025-09-26
Contact: Yu Xuechun, Email: xuechunyu2009@sina.com
Supported by:
State Administration of Traditional Chinese Medicine Key Research Office for the Treatment of Gastric Cancer Toxins (202261); Jiangsu Province Health Commission Project (Z2021035);Huai, an City Natural Science Research Plan Project (HABZ202215); Huai, an City Health Commission Science Fund Project (HAWJ202032)

摘要/Abstract

摘要：

目的　探讨（sirtuin 3，SIRT3）通过蛋白激酶B（Protein kinase B， AKT）信号通路调节食管鳞状细胞癌对顺铂敏感性的影响及可能的分子机制。方法　本实验实施时间为2023年5月至12月。通过在ECA109和KYSE30细胞中敲低SIRT3表达，两株细胞均分为SIRT3敲低的阴性对照组（shNC组）和SIRT3敲低的对照组（shSIRT3组）。Western blot检测各组细胞中SIRT3、AKT、磷酸化蛋白激酶B（p-AKT）及己糖激酶2（HK2）的蛋白表达水平；细胞计数试剂盒-8（CCK-8）检测顺铂对各组细胞活力的影响，并计算顺铂的半数抑制浓度（IC50）；平板克隆形成实验评估各组细胞对顺铂敏感性的影响。采用独立样本t检验进行统计分析。结果　ECA109细胞中shSIRT3组的IC50值低于shNC组［（6.65±0.45）μmol/L比（11.16±0.75）μmol/L，P<0.001］。KYSE30细胞中shSIRT3组的IC50值低于shNC组［（9.81±0.19）μmol/L比（15.53±1.11）μmol/L，P<0.001］。ECA109细胞中，在相同浓度顺铂下，shSIRT3组细胞的相对克隆形成率与shNC组比较（0.69±0.04比0.84±0.01、0.40±0.02比0.59±0.02、0.24±0.01比0.37±0.01、0.08±0.01比0.17±0.01），差异均有统计学意义（均P<0.05）。KYSE30细胞中，在低浓度顺铂（0.1 μmol/L和0.2 μmol/L）下，shSIRT3组相对克隆形成率与shNC组比较，差异均无统计学意义（均P>0.05）；高浓度顺铂（0.3 μmol/L和0.4 μmol/L）作用下，shSIRT3组细胞的相对克隆形成率与shNC组比较（0.41±0.01比0.66±0.06、0.14±0.01比0.50±0.02），差异均有统计学意义（均P<0.05）。在ECA109和KYSE30细胞中，shSIRT3组HK2、p-AKT蛋白的表达均低于shNC组（均P<0.01）。结论　沉默SIRT3表达可能通过AKT信号通路下调HK2表达，进而增强食管鳞状细胞癌对顺铂的敏感性。

关键词:

食管鳞状细胞癌, 沉默信息调节因子3, 顺铂抵抗, 蛋白激酶B

Abstract:

Objective To investigate the effect of silent information regulator 3 (SIRT3) on the sensitivity of esophageal squamous cell carcinoma to cisplatin through protein kinase B (AKT) signaling pathway and a the possible molecular mechanism. Methods The implementation period of this experiment was from May to December 2023. By knocking down SIRT3 expression in ECA109 and KYSE30 cells, the two cell lines were divided into a negative control group with SIRT3 knockdown (shNC group) and a control group with SIRT3 knockdown (shSIRT3 group). The protein expression levels of SIRT3, AKT, Phosphor-protein kinase B (p-AKT) and hexokinase 2 (HK2) in each group of cells were detected by Western blot; the effect of cisplatin on the viability of cells in each group was detected by Cell Counting Kit-8 (CCK-8), and the half inhibitory concentration (IC50) of cisplatin was calculated; the effect of each group of cells on cisplatin was evaluated by plate cloning assay. Statistical analysis was conducted using the independent sample t-test. Results The IC50 value of the shSIRT3 group in ECA109 cells was lower than that of the shNC group [(6.65 ± 0.45) μmol/L vs. (11.16 ± 0.75) μmol/L, P < 0.001]. In KYSE30 cells, the IC50 value of the shSIRT3 group was also lower than that of the shNC group [(9.81 ± 0.19) μmol/L vs. (15.53 ± 1.11) μmol/L, P < 0.001]. In ECA109 cells, under the same concentration of cisplatin, The relative clone formation rate of cells in the shSIRT3 group was compared with that in the shNC group (0.69±0.04 vs. 0.84±0.01, 0.40±0.02 vs. 0.59±0.02, 0.24±0.01 vs. 0.37±0.01, 0.08±0.01 vs. 0.17±0.01) (all P < 0.05). In KYSE30 cells, at low concentrations of cisplatin (0.1 μmol/L and 0.2 μmol/L), the relative clone formation rate in the shSIRT3 group was compared with that in the shNC group (all P > 0.05); Under the action of high-concentration cisplatin (0.3 μmol/L and 0.4 μmol/L), the relative clone formation rate of cells in the shSIRT3 group was compared with that in the shNC group (0.41±0.01 vs. 0.66±0.06 and 0.14±0.01 vs. 0.50±0.02) (both P < 0.05). In ECA109 cells and KYSE30 cells, the expressions of HK2 and p-AKT proteins in the shSIRT3 group were lower than those in the shNC group (all P<0.01) Conciusion Silencing SIRT3 expression may down-regulate HK2 expression through the AKT signaling pathway, thereby enhancing the sensitivity of esophageal squamous cell carcinoma to cisplatin.

Key words:

Esophageal squamous cell carcinoma, Sirtuin-3, Cisplatin-resistance, Protein kinase B

袁明亮陆羽叶欣杨希余学春.

SIRT3通过AKT信号通路调节食管鳞状细胞癌对顺铂的敏感性 [J]. 国际医药卫生导报, 2025, 31(18): 3058-3064.

Yuan Mingliang, Lu Yu, Ye Xin, Yang Xi, Yu Xuechun.

SIRT3 regulates the sensitivity of esophageal squamous cell carcinoma to cisplatin through the AKT signaling pathway [J]. International Medicine and Health Guidance News, 2025, 31(18): 3058-3064.

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SIRT3通过AKT信号通路调节食管鳞状细胞癌对顺铂的敏感性

SIRT3 regulates the sensitivity of esophageal squamous cell carcinoma to cisplatin through the AKT signaling pathway

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