School of Life Science and Technology, China Pharmaceutical University, Nanjing, PR China.
Immunol Lett. 2011 Dec 30;141(1):74-82. doi: 10.1016/j.imlet.2011.08.001. Epub 2011 Aug 30.
This study was aimed at evaluating the inhibitory effect of a polysaccharide that was isolated from Strongylocentrotus nudus eggs (SEP) against hepatocellular carcinoma in H22-bearing mice and elucidating its immunological mechanisms by determining its effects on the growth of transplanted tumors and immune response in H22-bearing mice. ICR mice inoculated with mouse hepatoma carcinoma cell lines H22 were treated with SEP at doses of 4, 8, 16 mg/kg/d for 12 days. The effects of SEP were measured via the growth of the transplanted tumors, splenocyte proliferation, T lymphocytes counts, CTL activity, the production of cytokines from splenocytes and the levels of serum Ig in tumor-bearing mice. In addition, the effects of SEP on Erk phosphorylation in mouse splenocytes and on the transcriptional activity of NFAT in Jurkat T cells were also investigated. Our results showed that SEP significantly inhibited the growth of transplanted tumors in mice. SEP could not only remarkably enhance splenocyte proliferation, CD4(+) and CD8(+) T cell numbers as well as CTL activity, but it also elevated IL-2 and TNF-α secretion as well as IgA, IgM and IgG levels in the serum. Furthermore, the activation of Erk phosphorylation and the NFAT promoter by SEP promoted the transcription and expression of downstream gene IL-2. In conclusion, our study demonstrates that SEP effectively inhibits hepatocellular carcinoma in vivo via enhancement of host immune system function, and it could be a potential therapeutic drug for hepatocarcinoma.
本研究旨在评估从海胆卵中分离得到的多糖（SEP）对荷肝癌 H22 小鼠的抑制作用，并通过测定其对荷瘤小鼠移植瘤生长和免疫反应的影响，阐明其免疫机制。将 ICR 小鼠接种小鼠肝癌细胞系 H22 后，用 SEP 以 4、8、16 mg/kg/d 的剂量处理 12 天。通过测量移植瘤的生长、脾细胞增殖、T 淋巴细胞计数、CTL 活性、脾细胞分泌细胞因子和荷瘤小鼠血清 Ig 水平来评估 SEP 的作用。此外，还研究了 SEP 对小鼠脾细胞中 Erk 磷酸化和 Jurkat T 细胞中 NFAT 转录活性的影响。结果表明，SEP 显著抑制了荷瘤小鼠移植瘤的生长。SEP 不仅能显著增强脾细胞增殖、CD4(+)和 CD8(+)T 细胞数量以及 CTL 活性，还能提高血清中 IL-2 和 TNF-α的分泌以及 IgA、IgM 和 IgG 的水平。此外，SEP 通过激活 Erk 磷酸化和 NFAT 启动子，促进下游基因 IL-2 的转录和表达。综上所述，本研究表明 SEP 通过增强宿主免疫系统功能有效抑制体内肝癌，可能是肝癌的一种潜在治疗药物。
