Z-guggulsterone reversed multi-drug resistance of hepatocarcinoma chemotherapy through down-regulating a PXR/P-gp pathway
- Author:
Huang-Shuai XIA
1
;
Hong-Bin XU
1
;
Zhuo-Lun YU
2
;
Qi-Hai ZHANG
2
;
Juan WANG
2
;
Wan-Ting XU
2
;
Hong-Bin XU
2
;
Hong-Bin XU
3
Author Information
- Publication Type:Journal Article
- Keywords: 5-Fu; DDP; guggulsterone; multi-drug resistance; P-gp; PXR
- From: Chinese Pharmacological Bulletin 2022;38(5):684-691
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the improved effects of Z-guggulsterone on the chemotherapy agents-induced proliferation and apoptosis through regulating PXR(pregnane X receptor)/P-gp(P-glycoprotein)signaling pathway in human hepatocellular carcinoma cells.Methods HepG2 cells were treated with Z-guggulsterone, DDP(cis-platinum)and 5-FU(5-fluorouracil)alone or in combination.CCK-8(Cell Counting Kit-8), Annexin-FITC/PI(Annexin V-fluorescein isothiocyanate isomer/propidium iodide)flow cytometry, RT-qPCR(Real-time quantitively Polymerase Chain Reaction)and Western blot were used to determine cell proliferation, apoptosis, the expression of MDR1 mRNA, PXR and P-gp respectively.Results Compared to DDP or 5-FU treatment alone, Z-guggulsterone(30 μmol·L-1)enhanced the inhibitory effects of DDP or 5-FU on the proliferation and apoptosis of HepG2 cells.Z-guggulsterone(30 μmol·L-1)also significantly reduced the expression levels of PXR,P-gp and MDR1 mRNA in HepG2 cells.Further research demonstrated that rifampicin, one agonist of PXR, increased the expression of PXR and P-gp, while Z-guggulsterone reversed its effects.Meanwhile, the expressions of PXR and P-gp were reduced by ketoconazole, one antagonist of PXR, and further decreased by co-administration with Z-guggulsterone.Conclusion Z-guggulsterone can improve the effects of chemotherapy on the proliferation and apoptosis of hepatocellular carcinoma cell lines by down-regulating the PXR/P-gp signaling pathway.
