The anti-hepatocellular carcinoma activity of Mel-P15 is mediated by natural killer cells
作者
Xu, T;Cui, TX;Peng, LP;Kong, S;Zou, JQ;Tian, XS
作者单位
[Xu, Tao; Cui, Tongxing; Peng, Lipan; Kong, Shuai; Zou, Jianqiang; Tian, Xingsong] Shandong Univ, Dept Hepatobiliary Surg, Prov Hosp, 324 Jing Wu Rd, Jinan 250021, Shandong, Peoples R China.
摘要
Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 mu g/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61.15% following treatment with 2 mg/kg Mel-P15. In addition, the immune response was activated following Mel-P15 treatment. Mel-P15 treatment increased the spleen and thymus indices, promoted splenocyte proliferation, stimulated NK cytotoxicity and upregulated the secretion of cytokines, including interleukin-2, interferon-gamma and tumor necrosis factor-a. In addition, the tumor inhibitory effect of Mel-P15 on BEL-7402-bearing nude mice was abrogated by the selective depletion of NK cells via the intraperitoneal injection of an anti-asialo GM-1 antibody. The results suggest that Mel-P15 inhibits tumor growth in vivo by promoting NK cell cytotoxicity. Mel-P15 may therefore be a potential immunotherapy candidate for the treatment of hepatocellular carcinoma.
关键词
ANTIMICROBIAL ACTIVITY; INTERFERON-GAMMA; IN-VIVO; MELITTIN; PEPTIDE; CANCER; RECOGNITION; APOPTOSIS; BACTERIA; INNATE
基本信息
