Regulatory mechanism of PESV on tumor-infiltrating natural killer cells in liver orthotopic transplantation tumor
10.3969/j.issn.1000-484X.2016.03.021
- VernacularTitle:蝎毒多肽提取物调控肝脏移植瘤中自然杀伤细胞浸润的机制研究
- Author:
Chen HAN
;
Zhaoxia WANG
;
Qing JIA
;
Zhaopeng WANG
;
Yueying ZHANG
;
Yu ZHANG
;
Hengxiao WANG
- Publication Type:Journal Article
- Keywords:
Scorpion venom;
Hepatocellular carcinoma;
Natural killer cells;
Perforin;
Granzyme B
- From:
Chinese Journal of Immunology
2016;32(3):390-395,400
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the regulatory mechanism of PESV on tumor-infiltrating natural killer ( NK) cells in a mice model with H22 orthotopic transplantation tumor .Methods:Suspensions of H22 cells were injected into the lobe of liver on C 57BL/6 mice for establishing liver orthotopic transplantation tumor model ,then the mice were randomly divided into four groups:normal group , control group ,PESV low dose group ( PESV-L ) and PESV high dose group ( PESV-H ) .Mice were either sacrificed for mechanistic studies or survival followed 14 days of therapy.The volume and weight of the tumor were measured .The proportion of infiltrating NK cells was measured by flow cytometry and the expression of NK 1.1(NK) cells was investigated by immunohistochemistry method .The expression of perforin and granzyme B were further investigated by real-time PCR.Results: In contrast to control group , the tumor inhibition rate was 15.38%and 30.77% in PESV-L group and PESV-H group respectively.The survival showed that PESV-H could significantly prolong the survival time of mice ,and life extension rate was 34.06%,(P<0.05).Histological analysis revealed significant pleomorphism of the neoplastic cells and invasive extendion in control group ,while there were more necrosis and less degree of atypia in PESV-L and PESV-H.The level of tumor-infiltrating NK cell was significantly higher in PESV-H than in tumor-bearing control group [(5.91±0.49)%vs.(3.69±0.50)%,P<0.05],and NK cells were infiltrating in peritumoral lesions.The mRNA of perforin and granzyme B in PESV-H were respectively 3.62 and 5.82 times than that of control group ( P<0.05 ) .Conclusion: These findings suggest that the treatment of PESV might increase the infiltration of natural killer cells in the orthotopic transplantation tumor and contribute to NK cells migration to the tumor , which induct and maintain the activities of natural killer cells against tumor cells by expressing perforin and granzyme B in vivo .
