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目的探讨海参硫酸软骨素(sea cucumber chondroitin sulfate,SC-CHS)对小鼠肿瘤生长和转移的抑制作用及其机制。方法建立C57 BL/6J小鼠Lewis肺癌自发性肺转移模型,连续腹腔注射给药21 d,剥离原位肿瘤和双侧肺,分别称瘤重和计数肺表面转移灶结节数;分离血清,ELISA法检测小鼠血清中肿瘤坏死因子-α(tumornecrosis factor-α,TNF-α)和γ-干扰素(γ-interferon,γ-IFN)的含量;采用RT-PCR法检测肿瘤组织中缺氧诱导因子(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、乙酰肝素酶(heparanase,Hpa)mRNA的表达。结果 SC-CHS可以显著抑制荷瘤小鼠肿瘤的生长,其平均抑制率为31.5%,并可以显著减少肺表面转移灶结节数(P<0.01),平均抑制率为42.3%;SC-CHS可以显著提高血清中TNF-α和γ-IFN的含量(P<0.05),降低荷瘤小鼠肿瘤组织中HIF-1α、VEGF、Hpa mRNA的表达(P<0.05)。结论 SC-CHS能显著抑制肿瘤细胞在小鼠体内的生长和转移,其机制可能与抑制肿瘤血管新生,提高机体免疫力有关。
Objective To investigate the inhibitory effect of sea cucumber chondroitin sulfate (SC-CHS) on tumor growth and metastasis in mice and its mechanism. Methods The model of spontaneous lung metastasis of Lewis lung carcinoma in C57 BL / 6J mice was established. The mice were inoculated intraperitoneally for 21 days, and the tumors in situ and the bilateral lungs were dissected. The nodules were counted as tumor weight and lung metastasis respectively. The contents of tumor necrosis factor-α (TNF-α) and γ-interferon (γ-IFN) in serum of mice were detected by ELISA. The levels of hypoxia The expression of Hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and heparanase (Hpa) mRNA were detected. Results SC-CHS could significantly inhibit tumor growth in tumor-bearing mice with an average inhibition rate of 31.5% and significantly reduce the number of metastatic lung nodules (P <0.01) with an average inhibition rate of 42.3%. SC-CHS (P <0.05), and decreased the expression of HIF-1α, VEGF and Hpa mRNA (P <0.05) in the tumor-bearing mice. Conclusion SC-CHS can significantly inhibit the growth and metastasis of tumor cells in mice. The mechanism may be related to the inhibition of tumor angiogenesis and the enhancement of immunity.