Objective To explore the possible action mechanism of Yangyin Jiedu Decoction（养阴解毒方） in the treatment of lung cancer. Methods Yangyin Jiedu Decoction with gradient concentrations of 0

62. 5

125

250

500 and 1000 μg/ml were added to A549 cells. The effects of different concentrations of Yangyin Jiedu Decoction at24

48 and 72 h on the proliferation of lung cancer cell line A549 were detected. Half maximal inhibitory concentration(IC

50

) was calculated based on cell survival rate

and A549 cells were divided into a control group and low-dose and high-dose groups of Chinese medicine. The control group used medium without Yangyin Jiedu Decoction. The high-dose group of Chinese medicine added the IC

50

concentration of Yangyin Jiedu Decoction for 48 h’s intervention.The low-dose group of Chinese medicine added 1/2 IC

50

concentration of Yangyin Jiedu Decoction for 48 h’s intervention. Cell cycle and apoptosis of each group were detected. ChIP-Seq technique was used to analyze the changes of whole genome modification of A549 cells treated with Yangyin Jiedu Decoction IC

50

concentration after 48 h’s intervention

and GO enrichment analysis was conducted. Results Yangyin Jiedu Decoction can significantly inhibit the proliferation of lung cancer cell A549 in a dose-dependent and time-dependent manner（P

<

0. 05）

and its IC

50

at48 h was 63 μg/ml. Low and high dose Chinese medicine group can block A549 cells in G2/M phase and induce the cell apoptosis

and the high dose Chinese medicine group was better than low dose Chinese medicine group in blocking and inducing advanced apoptosis and total apoptosis（P

<

0. 05）; Ch IP-Seq results showed that there were a total of 1058 genes H3K27Me3 modification changed

and 601 genes were increased in degree of modification

and 457 were reduced in degree of modification. GO analysis showed that the up-regulated genes were involved in biological functions such as G-protein coupled receptor signaling pathway and negative regulation of apoptosis process. Downregulated genes were involved in the positive regulation of RNA polymerase Ⅱ promoter transcription and neurological development. Conclusion 63 μg/ml Yangyin Jiedu Decoction can significantly inhibit the proliferation of A549 cells

keeping cell arrest in G2/M stage and induce apoptosis. The mechanism may be related to the alteration of H3K27Me3 epigenetic modification spectrum.