EP947 - Study On The Synergistic Effect And Mechanism Of SLBZD On PD-1 In The Treatment Of Colorectal Cancer Liver Metastasis

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Purpose/Background:

Objective: To analyze the synergistic effect and mechanism of Shenling Baizhu Decoction (SLBZD) on PD-1 in the treatment of colorectal cancer liver metastasis mice model using transcriptome sequencing technology (RNA-seq).

Methods/Interventions:

Methods: Thirty-two C57BL/6J mice were used to establish a colorectal cancer liver metastasis model by direct injection of spleen. The mice were randomly divided into four groups: PBS control group, PD1 monoclonal antibody group (αPD1), PD-1 monoclonal antibody combined with SLBZD low-dose group (αPD1+LD), and PD-1 monoclonal antibody combined with SLBZD high-dose group (αPD1+HD), with 8 mice in each group. The PD1+LD and PD1+HD groups were given 150 μl and 450 μl of concentrated SLBZD respectively, by gavage QD from the day of modeling for a total of 14 days; After the initiation of the drug administration, observe the fluorescence value once a week by using IVIS; The mice were sacrificed after the last administration. Liver metastasis tissues were taken from each group, total RNA was extracted, and transcriptome sequencing was performed using RNA-seq technology, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed, and differentially expressed genes were screened and validated.

Results/Outcomes:

Results: Compared with the blank group, all groups could reduce the number and volume of liver metastases in mice, and the PD1+HD group had the most obvious therapeutic effect. The RNA-seq sequencing results showed that there were 812 differentially expressed genes between the blank group and the PD1 group, including 275 up-regulated genes and 437 down-regulated genes; There were a total of 1163 differentially expressed genes between the PD1 group and the PD1+HD group, with 706 up-regulated genes and 457 down-regulated genes. Functional enrichment analysis showed that after treatment with Shenlingbaizhu Decoction combined with PDI, tumor-related pathways such as fatty acid metabolism, steroid metabolism, and lipid transport were significantly enriched.

Conclusion/Discussion:

Conclusion: SLBZD combined with PD-1 can improve the progression of colorectal cancer liver metastases in mice; PD-1 treatment has a synergistic effect on colorectal liver metastasis, and transcriptomic analysis suggests that it may be closely related to the intervention of fatty acid metabolism, steroid metabolism, and other related pathways.