Effects of Mitoxantrone liposomes on the proliferation，migration and stemness in ovarian cancer cells
- VernacularTitle:米托蒽醌脂质体对卵巢癌细胞增殖、迁移及干性的影响
- Author:
Dong WANG
1
;
Yue ZHANG
2
;
Baiwang CHU
3
;
Hua SUN
2
Author Information
1. Dept. of Pharmacy，Tianjin Medical University Cancer Institute & Hospital/National Clinical Research Center for Cancer/Tianjin Key Laboratory of Cancer Prevention and Therapy/Tianjin’s Clinical Research Center for Cancer，Tianjin 300060，China;Dept. of Pharmacy，Tianjin Cancer Hospital Airport Hospital，Tianjin 300308，China
2. College of Biotechnology，Tianjin University of Science & Technology，Tianjin 300457，China
3. Dept. of Pharmacy，Tianjin Cancer Hospital Airport Hospital，Tianjin 300308，China
- Publication Type:Journal Article
- Keywords:
mitoxantrone liposomes;
ovarian cancer;
cancer stem cells;
PI3K/AKT pathway
- From:
China Pharmacy
2026;37(1):42-48
- CountryChina
- Language:Chinese
-
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.
