Sun Hong-Xiang, Chen Li-Qing, Zhang Juan, Chen Feng-Yang
Key Laboratory of Animal Virology of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, China.
Key Laboratory of Animal Virology of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, China.
J Ethnopharmacol. 2014 May 14;153(3):831-9. doi: 10.1016/j.jep.2014.03.052. Epub 2014 Mar 29.
The larvae of Musca domestica (Diptera: Muscidae) have been used traditionally for malnutritional stagnation, decubital necrosis, osteomyelitis, ecthyma and lip scald and also to treat coma and gastric cancer in the traditional Chinese medicine. Its in vitro antitumor activity and immunomodulatory effect in naïve mice in relation to the traditional uses were also reported. However, the in vivo antitumor effect of this insect and its mechanism of action have not yet been well studied. The objectives of this study were to evaluate the in vivo antitumor potential of the peptide fraction from Musca domestica larvae (MDPF) and to elucidate its immunological mechanisms.
The mice inoculated with sarcoma S180 cells were orally administered with MDPF at three doses for 10 days. The effects of MDPF on the growth of mouse S180 sarcoma, splenocyte proliferation, the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), production and mRNA expression of cytokines from splenocytes, and serum antigen-specific antibody levels in tumor-bearing mice were measured.
MDPF could significantly not only inhibit the growth of mouse transplanted S180 sarcoma, but also promote splenocytes proliferation, NK cell and CTL activity from splenocytes, and enhance serum antigen-specific IgG, IgG2a and IgG2b antibody levels in S180-bearing mice. MDPF also significantly promoted the production of IFN-γ and up-regulated the mRNA expression levels of IFN-γ and Th1 transcription factors T-bet and STAT-4 in splenocytes from the S180-bearing mice. However, Th2 cytokine IL-10 and transcription factors GATA-3 and STAT-6 were not significantly changed both at transcriptional and protein levels following MDPF treatment.
MDPF significantly inhibit the growth of transplantable tumor in mice and its in vivo antitumor activity might be achieved by switching-on of Th1-based protective cell-mediated immunity. MDPF could act as antitumor agent with immunomodulatory activity.
家蝇（双翅目：蝇科）幼虫在传统中医中一直被用于治疗营养不良性停滞、褥疮坏死、骨髓炎、脓疱疮和唇烫伤，还用于治疗昏迷和胃癌。关于其传统用途，也有报道称其在体外对未接触过抗原小鼠的抗肿瘤活性和免疫调节作用。然而，这种昆虫的体内抗肿瘤作用及其作用机制尚未得到充分研究。本研究的目的是评估家蝇幼虫肽组分（MDPF）的体内抗肿瘤潜力，并阐明其免疫机制。
将接种肉瘤S180细胞的小鼠以三种剂量口服给予MDPF，持续10天。检测MDPF对小鼠S180肉瘤生长、脾细胞增殖、自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）活性、脾细胞细胞因子产生和mRNA表达以及荷瘤小鼠血清抗原特异性抗体水平的影响。
MDPF不仅能显著抑制小鼠移植性S180肉瘤的生长，还能促进脾细胞增殖、脾细胞NK细胞和CTL活性，并提高S180荷瘤小鼠血清抗原特异性IgG、IgG2a和IgG2b抗体水平。MDPF还显著促进IFN-γ的产生，并上调S180荷瘤小鼠脾细胞中IFN-γ以及Th1转录因子T-bet和STAT-4的mRNA表达水平。然而，MDPF处理后，Th2细胞因子IL-10以及转录因子GATA-3和STAT-6在转录和蛋白水平上均无显著变化。
MDPF能显著抑制小鼠移植瘤的生长，其体内抗肿瘤活性可能是通过开启基于Th1的保护性细胞介导免疫实现的。MDPF可作为具有免疫调节活性的抗肿瘤药物。
