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示,经Esc处理后,HL-60细胞中AKT蛋白的磷酸化水平 Anticancer activity of Neosetophomone B by targeting
和SKP2、MTH1蛋白表达水平降低,AKT上游效应信号 AKT/SKP2/MTH1 axis in leukemic cells[J]. Biochem
蛋白——p-PI3K 表达水平降低,AKT 下游效应信号蛋 Biophys Res Commun,2022,601:59-64.
白——P21、P27 表达水平均升高,表明 Esc 可通过抑制 [ 9 ] REN C,PAN R S,HOU L S,et al. Suppression of
AKT/SKP2/MTH1 通路来抑制 AML 细胞的恶性生物学 CLEC3A inhibits osteosarcoma cell proliferation and pro‐
motes their chemosensitivity through the AKT1/mTOR/
行为。同时,本研究在高浓度Esc基础上联合AKT激动
HIF1α signaling pathway[J]. Mol Med Rep,2020,21(4):
剂SC79进一步研究发现,HL-60细胞中以上蛋白的表达
1739-1748.
趋势均发生了逆转,且 Esc 抑制 HL-60 细胞增殖等的生
[10] YIN W,FU X,CHANG W W,et al. Antiovarian cancer
物学活性均受到不同程度的负面影响,这与 Sanjiv 等 [19]
mechanism of esculetin:inducing G0/G1 arrest and apopto‐
的研究具有相似性。 sis via JAK2/STAT3 signaling pathway[J]. J Pharm Phar‐
综上所述,Esc 可能是通过抑制 AKT/SKP2/MTH1 macol,2023,75(1):87-97.
通路,促进HL-60细胞中ROS的大量产生及细胞凋亡程 [11] 罗祥力,蔡芃夷,唐文 . 秦皮乙素对宫颈癌 SiHa 细胞增
序的启动,最终抑制 HL-60 细胞增殖。然而,本研究未 殖、迁移和侵袭的影响及机制[J]. 广西医学,2021,43
联合其他细胞株或原代细胞进行验证,也未开展动物实 (20):2430-2435.
验探讨其体内疗效,后续还需进一步深入研究。 [12] 马鑫. 秦皮乙素对肾透明细胞癌增殖、周期和凋亡的影
参考文献 响[J]. 临床泌尿外科杂志,2020,1(11):44-48.
[ 1 ] SHIMONY S,STAHL M,STONE R M. Acute myeloid [13] ZHU P,LI H,GE J,et al. Mechanism of USP11 regulated
leukemia:2025 update on diagnosis,risk-stratification, SIRT3/ROS in drug resistance of acute myeloid leukemia
and management[J]. Am J Hematol,2025,100(5): [J]. Clin Exp Med,2025,25(1):267.
860-891. [14] GERMON Z P,SILLAR J R,MANNAN A,et al. Bloc-
[ 2 ] SHORT N J,KONOPLEVA M,KADIA T M,et al. Ad‐ kade of ROS production inhibits oncogenic signaling in
vances in the treatment of acute myeloid leukemia:new acute myeloid leukemia and amplifies response to preci‐
drugs and new challenges[J]. Cancer Discov,2020,10 sion therapies[J]. Sci Signal,2023,16(778):eabp9586.
(4):506-525. [15] ZHOU H L,ZHOU L,GUAN Q,et al. SKP2-mediated
[ 3 ] BROWN L K,KANAGASABAI T,LI G L,et al. Co- MLKL degradation confers cisplatin-resistant in non-
targeting SKP2 and KDM5B inhibits prostate cancer pro‐ small cell lung cancer cells[J]. Commun Biol,2023,6
gression by abrogating AKT signaling with induction of (1):805.
senescence and apoptosis[J]. Prostate,2024,84(9): [16] ZHANG H P,JIANG R Y,ZHU J Y,et al. PI3K/AKT/
877-887. mTOR signaling pathway:an important driver and thera‐
[ 4 ] SHAO Y,REN W L,DAI H,et al. SKP2 contributes to peutic target in triple-negative breast cancer[J]. Breast
AKT activation by ubiquitination degradation of PHLPP1, Cancer,2024,31(4):539-551.
impedes autophagy,and facilitates the survival of thyroid [17] KUTTIKRISHNAN S,AHMAD F,MATEO J M,et al.
carcinoma[J]. Mol Cells,2023,46(6):360-373. Neosetophomone B induces apoptosis in multiple
[ 5 ] LI C S,XUE Y Y,WU J X,et al. MTH1 inhibition syner‐ myeloma cells via targeting of AKT/SKP2 signaling path‐
gizes with ROS-inducing agents to trigger cervical cancer way[J]. Cell Biol Int,2024,48(2):190-200.
cells undergoing parthanatos[J]. Biochim Biophys Acta [18] KUTTIKRISHNAN S,PRABHU K S,KHAN A Q,et al.
Mol Basis Dis,2024,1870(5):167190. Thiostrepton inhibits growth and induces apoptosis by tar‐
[ 6 ] REZOAN HOSSAIN M,ZAHRA SHOVA F T,AKTER geting FoxM1/SKP2/MTH1 axis in B-precursor acute
M,et al. Esculetin unveiled:decoding its anti-tumor poten‐ lymphoblastic leukemia cells[J]. Leuk Lymphoma,2021,
tial through molecular mechanisms:a comprehensive re‐ 62(13):3170-3180.
view[J]. Cancer Rep (Hoboken),2024,7(1):e1948. [19] SANJIV K,CALDERÓN-MONTAÑO J M,PHAM T M,
[ 7 ] MATHUR A,GANGWAR A,SALUJA D. Esculetin re‐ et al. MTH1 inhibitor TH1579 induces oxidative DNA
leases maturation arrest and induces terminal differentia‐ damage and mitotic arrest in acute myeloid leukemia[J].
tion in leukemic blast cells by altering the Wnt signaling Cancer Res,2021,81(22):5733-5744.
axes[J]. BMC Cancer,2023,23(1):387. (收稿日期:2025-09-17 修回日期:2025-12-17)
[ 8 ] KUTTIKRISHNAN S,BHAT A A,MATEO J M,et al. (编辑:林 静)
中国药房 2026年第37卷第1期 China Pharmacy 2026 Vol. 37 No. 1 · 41 ·

