Objective: To study the effect and mechanism of Xiaoai Jiedu decoction combined with cisplatin in inhibiting tumor growth of 4T1 tumor bearing mice. Method: BALB/c mice were subcutaneously inoculated with 4T1 breast cancer cells to establish the tumor bearing model. They were treated with cisplatin (CDDP

2 mg·kg-1) and Xiaoai Jiedu decoction (XJF

1×104 mg·kg-1) respectively

and the combination therapy. Body weight and tumor volume were quantified and recorded during drug treatment. The mice were put to death after 15 days

and tumor masses were stripped and weighed. The inhibition rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of heart

liver

spleen

kidney and tumor. The apoptosis of tumor cells was observed by TdT-mediated-dUTP nick end labeling (TUNEL) staining

and the apoptosis rate was counted. Western blot was used to detect the expressions of B-cell lymphoma-2(Bcl-2)

Bcl-2 related X protein(Bax)

lysine-specific demethylase 1(LSD1)

Histone H3

Histone H3K4me2 and Histone H3K9me2 in tumor tissues. Result: Compared with model group

the body weight of mice in the cisplatin group decreased

and the mice in the combined group had a higher body weight than those in cisplatin group (P<0.01). The combination therapy can further reduce the volume of transplanted tumor

improve the tumor inhibition rate

and promote the apoptosis rate of tumor cells significantly compared with cisplatin therapy (P<0.05

P<0.01). The expression of Bcl-2 in tumor tissues was up-regulated

and Bax was up-regulated (P<0.05

P<0.01). Each drug group could down regulate the protein expression of LSD1

and increase the methylation of histone H3K4 and H3K9

and the combination group showed the most significant effect on the protein expression (P<0.05

P<0.01). Conclusion: Xiaoai Jiedu prescription combined with cisplatin can obviously inhibit the growth of 4T1 tumor in tumor bearing mice. Its mechanism may be related to the down-regulation of histone demethylation enzyme level.