赤星衣酸甲酯的抗癌作用及机制研究

Anticancer effects and mechanism of methyl haematommate

目的探讨松萝Usnea diffracta中功效化合物赤星衣酸甲酯的体外抗癌活性及其作用机制。方法采用MTT法检测不同质量浓度的赤星衣酸甲酯对宣威肺癌XWLC-05细胞、肝癌HepG2细胞、乳腺癌MCF-7细胞的体外抗癌活性;以流式细胞技术分析赤星衣酸甲酯对HepG2细胞周期的调节作用;通过基因芯片技术分析赤星衣酸甲酯对MCF-7细胞基因表达的影响。结果赤星衣酸甲酯能够显著抑制XWLC-05、HepG2、MCF-7细胞的增殖,其体外抗癌作用具有明显的量效关系,对3株癌细胞的半数抑制浓度(IC_(50))分别为8.818、11.905、13.328μg/mL。赤星衣酸甲酯主要阻滞HepG2细胞于G_0/G_1期。基因芯片分析得到MCF-7细胞差异倍数大于1.5的mRNA有2 394个,其中1 605个下调,789个上调。结论赤星衣酸甲酯为首次从松萝中分离得到,且具有较强的抗癌活性,其作用机制可能与调节细胞周期和蛋白激酶信号通路有关。

Objective To study the in vitro inhibitory effect of methyl haematommate（a new bioactive compound in Usnea）, on the Xuanwei lung cancer cell line（XWLC-05）, Hepato carcinoma cell line（HepG2）, and breast carcinoma cell line（MCF-7）, and investigate its mechanism. Methods MTT assay was used to determine the inhibitory effect of methyl haematommate on the three cancer cell lines at different concentration（2, 4, 8, 16, and 32 μg/mL）. Cell cycle of HepG2 was analyzed by flow cytometry（FCM） and microarray assay was used to identify the differentially expressed gene profiles in MCF-7. Results MTT results showed that methyl haematommate could significantly inhibit the proliferation of cancer cells, and the inhibition was concentration-dependent. IC（50） values of the compound were 8.818, 11.905, and 13.328 μg/mL in XWLC, HepG2, and MCF-7 respectively. Cell cycle analysis indicated that methyl haematommate could arrest cancer cells at G0/G1. Totally 2 394 mRNAs were significantly regulated by the compound in MCF-7（fold change ≥ 1.5, P〈0.05）, of which 789 were up-regulated and 1 605 were down-regulated. Conclusion Methyl haematommate is isolated from Usnea diffracta for the first time, and it shows inhibitory effects on hunman cancer cell lines in vitro. MAPK pathway and G0/G1 arrest might contribute to the anticancer effects of methyl hematommate.