Study on Periplaneta americana Polypeptide PAE2 in Reversing Multidrug Resistance for Liver Cancer
10.13422/j.cnki.syfjx.20212523
- VernacularTitle:美洲大蠊多肽PAE2逆转肝癌多药耐药性
- Author:
Yin-rui LI
1
;
Hong LYU
1
;
Fang PENG
1
;
Ling OU
1
;
Ding-yu WU
1
Author Information
1. College of Pharmacy and Chemistry， The Laboratory Management Division， Dali University， Dali 671000， China
- Publication Type:Research Article
- Keywords:
Periplaneta americana polypeptide PAE2;
anti-tumor;
multi-drug resistance
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(5):52-61
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and mechanism of PAE2， a polypeptide of Periplaneta americana， in reversing multidrug resistance （MDR） for liver cancer in vivo. Method:Balb/c-nude mice were inoculated with HepG2 and HepG2/ADM cells under the armpits to establish animal models of liver cancer sensitive strains and animal models of MDR respectively. After successful modeling， the nude mice were randomly divided into normal group， HepG2 model group， HepG2/ADM model group， sorafenib group （positive drug control group， ig 30 mg·kg-1）， HepG2/ADM+PAE2 （iv） low， medium and high dose groups （50， 100， 200 mg·kg-1）， HepG2/ADM+PAE2 （ig） low， medium， and high dose groups （50， 100， 200 mg·kg-1）， skim cream group （ig 200 mg·kg-1）， and CⅡ-3 group （ig 200 mg·kg-1）， all of which received corresponding drug treatment. The body weight and tumor volume of nude mice were measured and recorded every 2 days. The next day after the last administration， tumor tissues of nude mice were taken to record the tumor weight. The effect of P. americana polypeptide PAE2 on permeability-glycoprotein（P-gp）， lung resistance protein（LRP） ， breast cancer resistance protein（BCRP）， protein kinase C（PKC）， glutathione S-transferase-π（GST-π）， topo-isomerase typeⅡ（ToPoⅡ）， multidurg resistance gene 1（MDR1） and Multidrug resistance-associated proteins（MRP1） of the protein level and gene level expression in tumor tissues were determined by immunohistochemistry （IHC） and real-time quantitative polymerase chain reaction （Real-time PCR）. In addition， both oral and intravenous administration groups were set up at the same time for preliminary study on the basic pharmacokinetic characteristics of P. americana polypeptide PAE2. Result:After the successful modeling， the body weight of the nude mice was significantly lower than that in the normal mice（P<0.05）. After treatment with corresponding drugs， the body weight increased to a certain extent， but it was still not as good as the normal nude mice. In iv administration， the medium-dose P. americana polypeptide PAE2 showed the best anti-tumor effect as compared with the model group （P<0.05）， while in oral administration， the anti-effect increased with the increase of the dose， so the high-dose group showed the best effect （P<0.05）. Preliminary crude extract CII-3 had no obvious anti-tumor effect， and skim cream showed a certain anti-tumor effect （P<0.05）. P. americana polypeptide PAE2 had certain effects on MDR related proteins and enzymes in vivo， mainly by inhibiting the expression of LRP and BCRP in tumor tissues and affecting the expression of these related proteins and genes to different degrees to inhibit intracellular drugs outflow， thereby promoting tumor apoptosis， and the effect was superior to that of the P. americana crude extract CⅡ-3 and skim cream. Conclusion:P. americana polypeptide PAE2 may reduce the drug efflux， promote intracellular drug accumulation and apoptosis by affecting the expression of related proteins and enzymes that mediate multidrug resistance， thereby exerting a reverse effect on HepG2/ADM cells Balb/c MDR in nude mice.
