Abstract: Objective To investigate the anti⁃tumor effect of PI3K inhibitor YY⁃20394 on diffuse large B⁃cell lymphoma (DLBCL) in vitro and the underlying mechanism. Methods The effects of different concentrations of YY⁃20394 on the proliferation of SU⁃DHL⁃4 cells (GCB subtybe) and U2932 cells (ABC subtype) were detected by CCK⁃8, and the IC₂₅, IC₅₀ and IC₇₅ at 24 h were calculated. The effects of different concentrations（IC₂₅、IC₅₀、IC₇₅） of YY⁃20394 on the apoptosis of SU⁃DHL⁃4 cells and U2932 cells were detected by flow cytometry. High⁃throughput RNA sequencing technology (RNA⁃Seq) was used to detect the changes of gene expression in cells before and after drug action, and the differentially expressed genes were analyzed by KEGG enrichment analysis and GO fumction annotation analysis. Gene expression data of each group of cells were analyzed by GSEA enrichment. Results Under the treatment of YY⁃20394, the proliferation inhibition rate and apoptosis rate of SU⁃DHL⁃4 cells increased (P<0.05), whereas the proliferation and apoptosis ability of U2932 cells changed insignificantly (P>0.05). The results of KEGG enrichment analysis and GO function annotation analysis showed that the anti⁃tumor effect of YY⁃20394 on SU⁃DHL⁃4 cells involved several signaling pathways, among which the activities of PI3K⁃AKT, AMPK and JAK⁃STAT signaling pathways were down⁃regulated, and might play a role in affecting cell biological functions such as alcohol synthesis, whereas U2932 cells were not enriched with significantly different signaling pathways. GSEA enrichment analysis showed that the activation level of PI3K⁃AKT signaling pathway in SU⁃DHL⁃4 cells was significantly lower than that of U2932 cells. Conclusions The PI3K inhibitor YY⁃20394 induces anti⁃tumor effects on the SU⁃DHL⁃4 cells of GCB subtype by affecting related signaling pathways such as PI3K⁃AKT, but does not significantly influence the U2932 cells of ABC subtype.

Key words: Diffuse large B-cell lymphoma')">Diffuse large B-cell lymphoma, PI3K inhibitor, YY-20394, PI3K-AKT signaling pathway, RNA-Seq