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米托蒽醌脂质体对卵巢癌细胞增殖、迁移及干性的影响
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| 篇名： | 米托蒽醌脂质体对卵巢癌细胞增殖、迁移及干性的影响 |
| TITLE： | Effects of Mitoxantrone liposomes on the proliferation，migration and stemness in ovarian cancer cells |
| 摘要： | 目的 探讨米托蒽醌脂质体（Lipo-MIT）对卵巢癌细胞增殖、迁移及癌症干细胞（CSCs）干性的影响，并基于磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）通路探讨其作用机制。方法通过体外实验考察Lipo-MIT对细胞增殖、迁移和CSCs干性特征的影响。构建裸鼠人卵巢癌细胞A2780异种移植瘤模型，探究2、5mg/kgLipo-MIT对荷瘤裸鼠安全性以及体内肿瘤生长、肿瘤组织病理特征的影响，并考察Lipo-MIT对细胞与肿瘤组织中PI3K/AKT通路、上皮-间充质转化、干性相关蛋白表达的调控作用。结果Lipo-MIT对A2780、SK-OV3和OV-CAR5细胞的半数抑制浓度分别为0.72、5.41、2.77μmol/L；与溶剂对照（0.1%二甲基亚砜）比较，0.5～2.5μmol/LLipo-MIT可显著降低细胞克隆形成率、缩短细胞迁移距离、减少迁移细胞数、下调神经钙黏素（N-cadherin）蛋白表达、上调上皮钙黏素（E-cadherin）蛋白表达（P＜0.05），并降低肿瘤球形成率、下调乙醛脱氢酶1A1（ALDH1A1）蛋白表达（P＜0.05）；1.0、2.5μmol/LLipo-MIT可显著降低干细胞成球概率和下调细胞中性别决定区Y框蛋白2表达（P＜0.05）。2、5mg/kgLipo-MIT对荷瘤裸鼠的体重、饮食量和饮水量及脏器（心、肝、脾、肺、肾）指数均无明显影响（P＞0.05），可显著改善肿瘤组织的病理变化，并可显著抑制肿瘤组织中N-cadherin和CD133、ALDH1A1（仅5mg/kgLipo-MIT）蛋白表达（P＜0.05），上调E-cadherin（仅5mg/kgLipo-MIT）蛋白表达（P＜0.05）。不同浓度/剂量Lipo-MIT均可显著降低细胞/肿瘤组织中PI3K、AKT蛋白的磷酸化水平（P＜0.05）。结论Lipo-MIT可通过抑制PI3K/AKT通路活性来抑制卵巢癌细胞的增殖、迁移和干性。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of Mitoxantrone liposomes （Lipo-MIT） on the proliferation， migration and cancer stem cell （CSCs） stemness of ovarian cancer cells， as well as to explore its mechanism of action based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） pathway. METHODS The effects of Lipo-MIT on cell proliferation， migration and the stemness characteristics of CSCs were investigated through in vitro experiments. A human ovarian cancer A2780 cells xenograft tumor model of nude mouse was established to explore the effects of Lipo-MIT at doses of 2 and 5 mg/kg on the safety of tumor-bearing mice， as well as in vivo tumor growth and the pathological characteristics of tumor tissues. The influence of Lipo-MIT on the expression levels of PI3K/AKT pathway-related proteins， epithelial-mesenchymal transition related proteins， and stemness related proteins in both cells and tumor tissues was also investigated. RESULTS The half maximal inhibitory concentrations of Lipo-MIT against A2780， SK-OV3， and OV-CAR5 cells were 0.72， 5.41， and 2.77 μmol/L， respectively. Compared with solvent control （0.1% dimethyl sulfoxide）， 0.5-2.5 μmol/L Lipo-MIT significantly reduced the cell colony formation rate， shortened the cell migration distance， decreased the number of migrated cells， down-regulated the protein expression of N-cadherin， up-regulated the protein expression of E-cadherin （P＜0.05）， and also decreased the stem cell sphere formation frequency and down-regulated the protein expression of aldehyde dehydrogenase 1A1 （ALDH1A1） （P＜0.05）. Additionally， 1.0 and 2.5 μmol/L Lipo-MIT significantly reduced the stem cell sphere formation probability and down-regulated the protein expression of sex determining region Y box protein 2 in cells （P＜0.05）. In vivo experimental results demonstrated that 2， 5 mg/kg Lipo-MIT had no significant effects on the body weight， food intake， water intake， and organ （heart， liver， spleen， lung， and kidney） indices of tumor-bearing nude mice （P＞0.05）， but could significantly improve the pathological changes of tumor tissues and remarkably inhibit the protein expressions of N-cadherin， CD133 and ALDH1A1（ only at 5 mg/kg Lipo-MIT）， up-regulate the expression of E- cadherin （only at 5 mg/kg Lipo-MIT） in tumor tissues （P＜0.05）. Lipo-MIT at different concentrations/doses significantly reduced the phosphorylation levels of PI3K and AKT proteins in cells/tumor tissues （P＜0.05）. CONCLUSIONS Lipo-MIT can inhibit the proliferation and migration of ovarian cancer cells and the stemness by suppressing the activity of the PI3K/AKT pathway. |
| 期刊： | 2026年第37卷第01期 |
| 作者： | 王冬；张悦；储百旺；孙华 |
| AUTHORS： | WANG Dong，ZHANG Yue，CHU Baiwang，SUN Hua |
| 关键字： | 米托蒽醌脂质体；卵巢癌；癌症干细胞；PI3K/AKT通路 |
| KEYWORDS： | mitoxantrone liposomes； ovarian cancer； cancer stem cells； PI3K/AKT pathway |
| 阅读数： | 79 次 |
| 本月下载数： | 0 次 |
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