Molecular Mechanism of Gypenoside L Inducing Ovarian Cancer Cell Apoptosis by Regulating NUF2 and Influencing Magnesium Homeostasis
10.13422/j.cnki.syfjx.20260611
- VernacularTitle:绞股蓝皂苷L调控NUF2影响镁稳态诱导卵巢癌细胞凋亡的分子机制
- Author:
Yang HONG
1
;
Di ZHANG
2
;
Yuanguang DONG
1
;
Jiaxin WANG
1
;
Lu PAN
1
;
Lijiang ZHOU
1
;
Mingdian YUAN
1
;
Qun WANG
1
;
Nan SONG
1
Author Information
1. Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847， China
2. Affiliated Hospital of Liaoning University of TCM， Shenyang 110032， China
- Publication Type:Journal Article
- Keywords:
gypenoside L;
ovarian cancer;
NDC80 kinetochore complex component （NUF2）;
magnesium homeostasis;
apoptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(13):155-165
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component （NUF2） and magnesium homeostasis in ovarian cancer cell apoptosis， as well as the regulatory mechanism of gypenoside L （Gyp-L） on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group， a low-concentration Gyp-L group （50 µmol·L-1）， a high-concentration Gyp-L group （100 µmol·L-1）， and a cisplatin （15 µmol·L-1） group. The migration， proliferation， and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays， clonal experiments， and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus （GEO） database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes （STRING） database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource （TIMER） database， and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis （GEPIA） database. The mRNA expression levels of NUF2， magnesium homeostasis-related indicators， such as magnesium transporter 1 （MAGT1）， non-imprinted in Prader-Willi/Angelman syndrome 1 （NIPA1）， NIPA-like domain containing 1 （NIPAL1）， as well as apoptosis-related indicators B cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） in OVCAR3 cells， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NUF2， MAGT1， NIPA1， NIPAL1， Bcl-2， and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed， and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning， TUNEL staining， Real-time PCR， and ProteinSimple WES. Finally， the Mg2+ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis （P<0.05）. Overexpression of NUF2 markedly increased the expression levels of MAGT1， NIPA1， NIPAL1， and Bcl-2， while reducing the expression level of Bax （P<0.05）. It also significantly elevated intracellular Mg2+ content and protein synthesis efficiency and simultaneously inhibited apoptosis （P<0.05）. Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2， downregulating the expression levels of NUF2， MAGT1， NIPA1， NIPAL1， and Bcl-2 （P<0.05）， while upregulating the expression level of Bax （P<0.05）. ConclusionGyp-L can inhibit the occurrence of ovarian cancer， and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.
