The mechanisms of paeonol reversing multidrug resistance in ovarian cancer SKOV3/DDP cells
10.16438/j.0513-4870.2018-0407
- VernacularTitle:丹皮酚逆转卵巢癌SKOV3/DDP细胞多药耐药性的机制
- Author:
Li HAN
1
;
Xiao-juan GUO
1
;
Zhong CHEN
2
;
Hua BIAN
1
;
Chao-yun ZHANG
1
;
Wen-hua ZANG
1
;
Qian WANG
1
;
Jiu-lue HU
1
Author Information
1. Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang 473004, China
2. College of Pharmaceutical Science, Soochow University, Suzhou 215123, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
paeonol;
ovarian cancer;
multidrug resistance;
metadherin;
phosphatase and tensin homolog
- From:
Acta Pharmaceutica Sinica
2018;53(9):1511-1517
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of this research is to investigate the effects and mechanisms of paeonol (PL), a phenolic compound found in many traditional Chinese formulations, on reversing drug resistance in the ovarian cancer resistant SKOV3/DDP cells. The results showed that PL had significant drug-resistant reversal effect on SKOV3/DDP cells. Flow cytometry showed that PL could inhibit P-glycoprotein (P-gp) function in a concentration-dependent manner. Fluorescent quantitative PCR and cell immunofluorescence techniques were used to detect mechanisms of action. Results revealed that both the inhibitory effect on MDR1/P-gp and metadherin (MTDH) expression and the induction effect on phosphatase and tensin homolog (PTEN), by 15, 30, and 60 μmol·L-1 PL, were increased with increased concentrations of PL (P < 0.01, P < 0.05). The inhibitory effect on MTDH mRNA and the induction effect on PTEN mRNA, by PI3K inhibitor LY294002, were stronger or equivalent to that of the 60 μmol·L-1 PL treated group; however, the inhibition or induction effect on MTDH or PTEN protein were only comparable to the 15 μmol·L-1 PL treated group. The present study shows that the effect of PL on SKOV3/DDP cells may be related to the inhibition of P-gp function and expression, the inhibition of MDR1, MTDH expression, and the induction of PTEN expression, all which can provide a theoretical foundation for PL as a drug resistance reversal agent on the treatment of ovarian cancer chemotherapy resistance.
