海参硫酸软骨素抑制小鼠Lewis肺癌生长和转移作用的研究

THE ANTI-METASTASIS EFFECT OF CHONDROITIN SULFATE ISOLATED FROM ISOSTICHOPUS BADIONOTUS ON SPONTANEOUS METASTASIS OF MOUSE LEWIS LUNG CARCINOMA AND ITS MECHANISM

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 explore the inhibitory effect of sea cucumber chondroitin sulfate （SC-CHS） isolated from Isostichopus badionotus on growth and metastasis of Lewis lung carcinoma in mice. Method The Lewis lung carcinoma models of C57BL/6J mice were established. Different treatments were served from day 2 after transplantation and all mice were sacrificed after 21 d. The subcutaneous tumors were weighed to calculate the inhibitory rate. The metastatic tumor foci on lung surface in mice were counted to calculate the occurrence rate and inhibitory rate of metastases on lung surface. The expression of HIF-1α, VEGF and Hpa mRNA were detected by RT-PCR. ELISA were used to estimated TNF-ct and T-IFN in the serum. Results The tumor growth was suppressed significantly in SC-CHS low and high groups, and the average inhibition rate was 31.5% compared with control group. The metastatic foci occurrence rate of the SC-CHS group were lower than control group, and the difference was significant. SC-CHS could significantly down-regulate the expression levels of HIF-1α, VEGF and Hpa mRNA than control. And SC-CHS also could increase amounts of TNF-α and γ-IFN in serum. Conclusion SC-CHS has inhibitory effect on growth and metastasis of Lewis lung carcinoma cell in mice, and may be through inhibiting solid tumor angiogenesis and improving the immunity in mice.