目的 研究desmosdumotin-C（Des-C）B環(huán)對位氟修飾衍生物TPP對人乳腺癌細(xì)胞MCF-7的增殖抑制作用，并探討其作用機(jī)制。方法 MTT法檢測質(zhì)量濃度為1.0、2.5、5.0、10.0、20.0 μg/mL的TPP作用48 h后，對MCF-7細(xì)胞的增殖抑制率；流式細(xì)胞術(shù)檢測20.0 μg/mL TPP作用0、24、48 h誘導(dǎo)MCF-7細(xì)胞的凋亡程度；流式細(xì)胞術(shù)檢測20.0 μg/mL TPP作用0、24、48 h對MCF-7細(xì)胞中NF-κB P65陽性細(xì)胞表達(dá)率的影響。結(jié)果 作用48 h后，2.5、5.0、10.0、20.0 μg/mL的TPP對MCF-7細(xì)胞增殖均有顯著抑制作用，且抑制率隨著濃度的升高而增大；20 μg/mL TPP作用24、48 h均可誘導(dǎo)細(xì)胞凋亡；作用48 h后，20 μg/mL TPP可顯著減少M(fèi)CF-7中NF-κB P65陽性細(xì)胞率。結(jié)論 TPP顯著抑制MCF-7細(xì)胞增殖，誘導(dǎo)MCF-7細(xì)胞凋亡，作用機(jī)制可能與下調(diào)NF-κB表達(dá)有關(guān)。

Objective To study the inhibitory effects of TPP, a desmosdumotin-C B ring para-fluoro modified derivative, on human breast cancer MCF-7 cell proliferation, and investigate the possible mechanisms.Methods MTT assay was used to measure the proliferation suppression of MCF-7 cells after treated with 1.0, 2.5, 5.0, 10.0, and 20.0 μg/mL TPP for 48 h, and then the cell apoptosis rate and expression rate of NF-κB P65 positive cells were tested by flow cytometry after 20.0 μg/mL TPP treatment for 0, 24, and 48 h.Results MTT assay showed that, after treatment for 48 h, 1.0, 2.5, 5.0, 10.0, and 20.0 μg/mL TPP all exhibited the inhibitory effects and showed a dose-dependent relationship. Flow cytometry results showed that 20.0 μg/mL TPP induced cell apoptosis after treatment for 24 and 48 h. TPP (20.0 μg/mL) significantly reduced the rate of NF-κB P65-positive cells in MCF-7 cells after treatment for 48 h.Conclusion TPP could inhibit the proliferation of MCF-7 cells, which may be induced by cell apoptosis. Down-regulation of NF-κB is possible to be related with apoptosis.

國家自然科學(xué)基金項(xiàng)目（81072546；81470156）