Induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 through regulating the Fas/FasL sig-naling pathway and the inhibitory effect on the growth of transplanted tumor in nude mice
- VernacularTitle:重楼皂苷Ⅸ通过调节Fas/FasL信号通路诱导肝癌细胞凋亡及对裸鼠移植瘤生长的抑制作用
- Author:
Minna YAO
1
;
Wei ZHANG
1
;
Kai GAO
1
;
Ruili LI
1
;
Ying YIN
1
;
Chao GUO
1
;
Yunyang LU
2
;
Haifeng TANG
2
;
Jingwen WANG
1
Author Information
1. Dept. of Pharmacy，Xijing Hospital of Air Force Medical University，Xi’an 710032，China
2. Dept. of Chinese Materia Medica and Natural Medicines，School of Pharmacy，Air Force Medical University，Xi’an 710032，China
- Publication Type:Journal Article
- Keywords:
polyphyllin 9;
hepatocellular carcinoma
- From:
China Pharmacy
2025;36(18):2238-2243
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.
