目的 探討3-O-(3-甲氧基肉桂酰)-甘草次酸酯對(duì)HepG2細(xì)胞體外抑制作用及其作用機(jī)制。方法 采用MTT法考察藥物對(duì)肝癌細(xì)胞HepG2、宮頸癌細(xì)胞HeLa、結(jié)腸癌細(xì)胞HT-29、心肌細(xì)胞H9C2、犬腎上皮細(xì)胞MDCK和血管內(nèi)皮細(xì)胞HY926的細(xì)胞毒性，利用細(xì)胞染色法觀察不同濃度3-O-(3-甲氧基肉桂酰)-甘草次酸酯對(duì)HepG2細(xì)胞形態(tài)的影響，流式細(xì)胞術(shù)評(píng)價(jià)該化合物誘導(dǎo)HepG2細(xì)胞的凋亡。結(jié)果 3-O-(3-甲氧基肉桂酰)-甘草次酸酯具有較好的抑制HepG2細(xì)胞增殖活性作用，其半數(shù)有效抑制濃度（IC₅₀）為8.28 μmol/L，明顯強(qiáng)于甘草次酸的活性（IC₅₀>50 μmol/L）。3-O-(3-甲氧基肉桂酰)-甘草次酸酯及其合成原料甘草次酸、3-甲氧基肉桂酸對(duì)非腫瘤細(xì)胞MDCK、HY926、H9C2細(xì)胞毒性較弱（IC₅₀>24 μmol/L）。3-O-(3-甲氧基肉桂酰)-甘草次酸酯濃度在12.5 μmol/L時(shí)，對(duì)MDCK、HY926、H9C2細(xì)胞抑制率分別為17.05%、16.08%、4.66%，與對(duì)HepG2細(xì)胞的抑制效果相比差異明顯。不同濃度3-O-(3-甲氧基肉桂酰)-甘草次酸酯對(duì)HepG2細(xì)胞Giemsa染色、H33342染色的細(xì)胞形態(tài)有明顯差異。隨著3-O-(3-甲氧基肉桂酰)-甘草次酸酯濃度的升高，早期凋亡率逐漸增加，而晚期凋亡率無明顯變化，提示3-O-(3-甲氧基肉桂酰)-甘草次酸酯可以有效地誘導(dǎo)細(xì)胞早期凋亡，并呈現(xiàn)一定的量效關(guān)系。結(jié)論 3-O-(3-甲氧基肉桂酰)-甘草次酸酯具有良好的抗腫瘤作用，對(duì)HepG2細(xì)胞抑制效果最好，對(duì)非癌細(xì)胞MDCK、HY926、H9C2沒有明顯抑制效果，該作用主要通過誘導(dǎo)HepG2細(xì)胞凋亡，且呈現(xiàn)一定的量效關(guān)系。

Objective To study the inhibitory effect of 3-O-(3-methoxy cinnamoyl)-glycyrrhetinic acid ester against HepG2 cells in vitro and explore its mechanism. Methods Cytotoxicities of 3-O-(3-methoxy cinnamoyl)-glycyrrhetinic acid ester against three tumour cells lines (HepG2, HeLa, HT-29) and three normal cell lines (H9C2, MDCK, and HY926) were detected by MTT assay. Effects of various concentration of 3-O-(3-methoxy cinnamoyl)-glycyrrhetinic acid ester on morphological changes of HepG2 cells were investigated by Giemsa staining and H3334 staining. Apoptosis of HepG2 cells induced by the compound was evaluated by flow cytometry. Results 3-O-(3-Methoxy cinnamoyl)-glycyrrhetinic acid ester had better inhibition of HepG2 cell proliferation activity with IC₅₀ of 8.28 μmol/L than that (IC₅₀>50 μmol/L) of glycyrrhetinic acid. 3-O-(3-Methoxy cinnamoyl)-glycyrrhetinic acid ester and its precursor drugs glycyrrhetinic acid and (3-methoxy) cinnamoyl acid had weak cytotoxicities against MDCK, HY926, and H9C2 cells. The inhibitory rates of 3-O-(3-methoxy cinnamoyl)-glycyrrhetinic acid ester at concentration of 12.5 μmol/L against MDCK, HY926, and H9C2 cells were 17.05%, 16.08%, and 4.66%, which had significant differences compared with the inhibitory effects on HepG2 cells. There were obvious differences on morphological changes of HepG2 cells at various concentration of 3-O-(3-methoxy cinnamoyl)-glycyrrhetinic acid ester stained by Giemsa staining and H3334 staining methods. With 3-O-(3-methoxy cinnamoyl)-glycyrrhetinic acid ester concentration increased, the early apoptosis rate increased gradually, but had no obvious change rate of late apoptosis, and the results showed that the drug effectively induced HepG2 cell apoptosis, with dose-dependent relationship. Conclusion 3-O-(3-Methoxy cinnamoyl)-glycyrrhetinic acid ester displays good anti-tumor effect, which has a considerable inhibition against HepG2 but low toxicity effect on normal cells MDCK, HY926, and H9C2. Its mechanism may be related to apoptosis of HepG2 cells, and has a dose-response relationship.

國家自然科學(xué)基金資助項(xiàng)目（81173519）；北京市與中央在京高校共建項(xiàng)目（BJGJ1528）；北京中醫(yī)藥大學(xué)創(chuàng)新團(tuán)隊(duì)資助項(xiàng)目（2011-CXTD-15）