目的 研究西黃丸醇提液抑制荷4T1小鼠乳腺癌腫瘤的生長(zhǎng)及作用機(jī)制。方法 建立荷4T1小鼠乳腺癌模型，以低、中、高劑量（0.39、0.78、1.95 g/kg）ig給予西黃丸醇提液2周，分離腫瘤組織，稱(chēng)質(zhì)量并計(jì)算抑瘤率；體外培養(yǎng)4T1乳腺癌細(xì)胞株，加入低、中、高濃度（1.25、2.50、5.00 μg/mL）的西黃丸醇提液作用48 h，CCK-8法檢測(cè)細(xì)胞增殖抑制率；TUNEL染色檢測(cè)細(xì)胞凋亡；實(shí)時(shí)熒光定量PCR（qRT-PCR）法檢測(cè)4T1細(xì)胞中FXR mRNA表達(dá)，Western Blotting檢測(cè)法尼酯受體（FXR）蛋白表達(dá)。結(jié)果 與模型組比較，西黃丸醇提液低、中、高劑量組荷瘤質(zhì)量均明顯下降（P<0.05），且呈劑量相關(guān)性；CCK-8結(jié)果顯示，作用48 h，4T1細(xì)胞的增殖抑制率隨西黃丸醇提液濃度的升高而增加，高濃度組可達(dá)43.13%；TUNEL熒光染色結(jié)果顯示，與對(duì)照組比較，西黃丸醇提液低、中、高濃度組4T1細(xì)胞凋亡數(shù)量顯著增加（P<0.05）；qRTPCR、Western Blotting結(jié)果顯示，4T1細(xì)胞中FXR mRNA、蛋白表達(dá)水平隨西黃丸醇提液濃度的升高顯著上調(diào)，且低、中、高濃度組差異均具有統(tǒng)計(jì)學(xué)意義（P<0.05）。結(jié)論 西黃丸可能通過(guò)激活FXR受體促進(jìn)腫瘤細(xì)胞凋亡從而抑制腫瘤生長(zhǎng)。

Objective To study the effect of alcohol extract of Xihuang Pill on the growth of 4T1 mouse breast cancer and its possible mechanism. Methods We established a 4T1 mouse breast cancer model. Model mice were administered with alcohol extract of Xihuang Pill at low, medium and high doses for two weeks. Tumor tissues were then removed and weighed, and the tumor inhibition rate was calculated. The 4T1 breast cancer cell line was cultured in vitro. The ethanol extract of Xihuang pill with low, medium and high concentration (1.25, 2.50, 5.00 μg/mL) were added for 48 hours. Tumor cell activity was detected by CCK-8. The apoptosis of tumor cells was detected by TUNEL staining. The mRNA expression of farnesoid X receptor (FXR) in tumor tissue was detected by qRT-PCR and their protein expression levels were detected by Western Blotting. Results Compared with model group, tumor volumes and tumor weights in the alcohol extract of Xihuang Pill groups decreased significantly with increasing doses of Xihuang Pill, there were significant differences among low, medium and high concentration groups (P<0.05). CCK -8 results showed that the inhibition rate of tumor cells proliferation was increased with the increase of dose of alcohol extract of Xihuang Pill at 48 h, and that of the high dose group reached 43.13%. TUNEL staining showed that the number of apoptotic tumor cells increased with increasing doses of alcohol extract of Xihuang Pill. qRT-PCR and Western Blotting showed that mRNA and protein expression of FXR in tumor cells increased with increasing doses of alcohol extract of Xihuang pill. There were significant differences among low, medium and high concentration groups (P<0.05). Conclusion Xihuang Pill might promote tumor cell apoptosis and further inhibit the tumor growth of 4T1 mouse breast cancer. The mechanism may be related to upregulation of FXR.

R962.2;R287.4

國(guó)家自然科學(xué)基金項(xiàng)目（81573664）