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目的通过检测土木香中3种倍半萜内酯化合物异土木香内酯(isoalantolactone,1),2-羟基-11,13-二氢异土木香内酯(2-hydroxy-11,13-dihydroisoalantolactone,2)和11,13-二氢异土木香内酯(11,13-dihydroisoalan-tolactone,3)抗肿瘤活性,探讨化合物的构效关系。方法利用MTT比色法检测3种倍半萜内酯化合物对人肺肿瘤细胞增殖活性的影响;以移植性小鼠肝癌H22为模型,检测异土木香内酯对在体肿瘤生长以及机体免疫能力的影响;以体外培养的仓鼠肺成纤维细胞(CHL)为对象,评价异土木香内酯对正常细胞的毒性。结果化合物1(异土木香内酯)对人非小细胞肺肿瘤细胞(A549、RERF-LC-jk、QG-56)的增殖抑制作用强于顺铂,对人小细胞肺肿瘤细胞(PC-6和QG-90)的增殖抑制作用与顺铂相同,而化合物2和3对各种实验用肿瘤细胞的增殖增不显示抑制活性;化合物1对肝癌H22生长具有较强的抑制活性,但对小鼠胸腺指数和脾指数的影响与对照组相比均没有显著差异;化合物1对体外培养的CHL细胞显示较弱的毒性。结论化合物1显示较强的体内外抗肿瘤活性,而化合物2和化合物3对体内外肿瘤的生长均不显示抑制活性,说明体内外抗肿瘤活性可能与其具有的α,β-不饱和五元内酯环的结构有关,不饱和的环外双键氢化饱和后形成的饱和五元内酯环,可能是体内外抗肿瘤活性消失或减弱的原因;增强机体免疫力是其抗肿瘤作用的机制。
OBJECTIVE To investigate the effects of three sesquiterpene lactone compounds isoalantolactone (1), 2-hydroxy-11,13-dihydroisoalantolactone , 2) and 11,13-dihydroisoalan-tolactone (3), and to explore the structure-activity relationship of the compounds. Methods MTT colorimetric assay was used to detect the effects of three sesquiterpene lactones on the proliferation of human lung cancer cells. The transplanted mouse hepatoma H22 was used as a model to detect the effects of isohumuleol on tumor growth and immune capacity ; In vitro cultured hamster lung fibroblasts (CHL) as the object, the evaluation of isohumulone lactate normal cell toxicity. Results The inhibitory effect of compound 1 (isomerism) on the proliferation of human non-small cell lung cancer cells (A549, RERF-LC-jk, QG-56) 6 and QG-90) showed the same inhibitory effect on proliferation as that of cisplatin, while compounds 2 and 3 did not show any inhibitory activity on proliferation of various experimental tumor cells. Compound 1 showed a strong inhibitory activity on the growth of H22 tumor, The effect of mouse thymus index and spleen index was not significantly different from that of the control group. Compound 1 showed weaker toxicity to cultured CHL cells. Conclusion Compound 1 showed strong antitumor activity in vitro and in vivo, while compound 2 and compound 3 showed no inhibitory activity on tumor growth in vitro and in vivo, indicating that antitumor activity in vitro and in vivo may be related to their α, β-unsaturated five-membered The structure of the ester ring is related to the saturated five-membered lactone ring formed by the saturation of the unsaturated exocyclic double bond, which may be the reason for the disappearance or weakening of antitumor activity in vivo and in vitro. The enhancement of the immunity of the body is a mechanism of its anti-tumor effect.