目的 探討澤蘭葉黃素調(diào)節(jié)CXC趨化因子配體12（CXCL12）/CXC趨化因子受體4（CXCR4）信號(hào)軸對(duì)肺癌細(xì)胞增殖、遷移和侵襲的影響。方法 體外培養(yǎng)A549細(xì)胞，用不同濃度（0、5、10、20、40、80 mmol/L）澤蘭葉黃素處理，篩選藥物作用濃度。將細(xì)胞分對(duì)照組、澤蘭葉黃素（10、20、40 mmol/L）組、澤蘭葉黃素＋CXCL12組。采用平板克隆法檢測(cè)A549細(xì)胞增殖情況；通過(guò)劃痕愈合率觀察細(xì)胞遷移；采用Western blotting法檢測(cè)CXCL12、CXCR4、G1/S-特異性周期蛋白-D1（CyclinD1）、基質(zhì)金屬蛋白酶（MMP）-2、MMP-9蛋白表達(dá)。通過(guò)建立裸鼠移植瘤模型，考察澤蘭葉黃素對(duì)裸鼠移植瘤的生長(zhǎng)和組織內(nèi)相關(guān)蛋白表達(dá)的影響。結(jié)果 選定10、20、40 µmol/L為澤蘭葉黃素作用濃度進(jìn)行后續(xù)實(shí)驗(yàn)；與對(duì)照組比較，澤蘭葉黃素組A549細(xì)胞克隆率、劃痕愈合率和侵襲數(shù)目顯著下降，CXCL12、CXCR4、CyclinD1、MMP-2、MMP-9蛋白表達(dá)顯著下調(diào)（P＜0.05）；與澤蘭葉黃素40 μmol/L組比較，澤蘭葉黃素＋CXCL12組細(xì)胞克隆率、劃痕愈合率和侵襲數(shù)目增加，CXCL12、CXCR4、CyclinD1、MMP-2和MMP-9蛋白表達(dá)顯著上調(diào)（P＜0.05）。裸鼠移植瘤實(shí)驗(yàn)顯示，與對(duì)照組比較，澤蘭葉黃素組裸鼠移植瘤質(zhì)量和體積下降，移植瘤組織內(nèi)CXCL12和CXCR4蛋白表達(dá)顯著下調(diào)（P＜0.05）。結(jié)論 澤蘭葉黃素可能通過(guò)抑制CXCL12/CXCR4信號(hào)軸蛋白表達(dá)，抑制肺癌細(xì)胞增殖、遷移和侵襲速度。

Objective To investigate the effects of eupafolin on proliferation, migration, and invasion of lung carcinoma cells by regulating the CXCL12/CXCR4 signaling axis. Methods A549 cells were cultured in vitro and treated with different concentrations (0, 5, 10, 20, 40, 80 mmol/L) of eupafolin to screen for drug action concentrations. The cells were devided into control group, eupafolin (10, 20, 40 μmol/L) group, and eupafolin + CXCL12 group. Plate cloning method was applied to detect the proliferation of A549 cells. Scratch healing rate was applied to observe cell migration. Western blotting method was applied to detect the protein expression of CXCL12, CXCR4, CyclinD1, MMP-2, and MMP-9. A nude mouse transplantation tumor model was established, and the effects of eupafolin on the growth of nude mouse transplantation tumors, and the expression of tissue related proteins were investigated. Results 10, 20, and 40 µmol/L were selected as the effective concentrations of eupafolin for subsequent experiments. Compared with control group, the cloning rate, scratch healing rate, and invasion number of A549 cells in the eupafolin groups were decreased, the protein expression of CXCL12, CXCR4, CyclinD1, MMP-2, and MMP-9 were downregulated (P < 0.05). Compared with eupafolin 40 µmol/L group, the cloning rate, scratch healing rate, and invasion number of A549 cells in eupafolin + CXCL12 group were increased, and the protein expression of CXCL12, CXCR4, CyclinD1, MMP-2, and MMP-9 were upregulated (P < 0.05). The experiment of nude mouse transplantation showed that compared with the control group, the quality and volume of the transplanted tumor in the eupafolin group decreased, and the expression of CXCL12 and CXCR4 proteins in the transplanted tumor tissue was downregulated (P < 0.05). Conclusion Eupafolin may inhibit the proliferation, migration, and invasion rate of lung carcinoma cells by inhibiting the expression of CXCL12/CXCR4 signaling axis proteins.

R966

邯鄲市科學(xué)技術(shù)研究與發(fā)展計(jì)劃（21422083138）