香菇多糖对结肠癌荷瘤小鼠抗肿瘤作用的实验研究

An experimental study on the anti-tumor effects of lentinan on mice bearing colon cancer

目的:观察香菇多糖对结肠癌荷瘤小鼠血清中内皮细胞生长因子(Vascular Endothelial Growth Factor,VEGF)、肿瘤转移抑制基因(Tumor metastasis suppressor gene,nm23基因)、白细胞介素(Interleukin,IL)-2、IL-4、IL-10、γ干扰素(Interferonγ,IFN-γ)、基质金属蛋白酶(Matrix Metalloproteinase,MMP)2和MMP7的含量及瘤组织中Bcl-2 associated X的蛋白质(Bax)、B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、含半胱氨酸的天冬氨酸蛋白水解酶3(Cysteine-containing Aspartate Proteolytic Enzyme 3,Caspase3)和含半胱氨酸的天冬氨酸蛋白水解酶9(Caspase9)基因表达的影响,分析其抑制肿瘤的作用及机制。方法:40只裸鼠于左腋下部接种HCT116结肠癌细胞悬液制作荷瘤小鼠模型,随机分成5组,即模型组,香菇多糖高、中、低剂量组,环磷酰胺(CTX)组,采用酶联免疫吸附测定(ELISA)法检测各组小鼠血清中VEGF、nm23、IL-2、IL-4、IL-10、IFN-γ、MMP2和MMP7的含量变化;qRT-PCR技术检测Bax、Bcl-2、Caspase3和Caspase9基因表达情况。结果:高、中、低剂量的香菇多糖可增加脾脏指数,抑制移植瘤生长;可减少小鼠血清中VEGF、MMP2和MMP7的含量,同时能提高血清中nm23、IL-2、IL-4、IL-10、IFN-γ的含量;可增加Bax、Caspase3和Caspase9的基因表达,减少Bcl-2基因表达;在香菇多糖中剂量组中,上述变化最为明显。结论:香菇多糖可能通过调节小鼠血清中上述细胞因子增强免疫功能及促进瘤细胞凋亡,从而达到抑制荷瘤生长和转移的效果。

Objective:To observe the effects of lentinan on the content of VEGF,nm23,IL-2,IL-4,IL-10,IFN-γ,MMP2 and MMP7 in the serum and expression of Bax,Bcl-2,Caspase3,Caspase9 genes in tumor tissue of colon cancer tumor-bearing mice,and analyze its tumor-inhibiting effects and mechanisms.Methods:40 nude mice were inoculated with HCT116 colon cancer cell suspension in the left axilla to make tumor-bearing mouse models.40 mouse models were randomly divided into 5 groups,namely the control group,the high,medium and low dose lentinan groups,and the CTX group.The serum levels of VEGF,nm23,IL-2,IL-4,IL-10,IFN-γ,MMP2 and MMP7 of mice in each group were detected by ELISA method.The expression of Bax,Bcl-2,Caspase3 and Caspase9 genes was detected by qRTPCR method.Results:High,medium and low doses of lentinan can increase the spleen indexes and inhibit the growth of transplanted tumors,reduce the levels of VEGF,MMP2 and MMP7 in the serum of mice,increase the levels of nm23,IL-2,IL-4,IL-10 and IFN-γin the serum,increase the gene expression of Bax,Caspase3 and Caspase9,and reduce the expression of Bcl-2 gene.In the medium dose lentinan group,the above changes were most obvious.Conclusion:Lentinan may enhance immune function and promote tumor cell apoptosis by regulating the above-mentioned cytokines in mouse serum,thereby achieving the effect of inhibiting tumor growth and metastasis.