Luo Cancan, et al., Second Affiliated Hospital of Nanchang University: HDAC inhibitor cedabenamide combined with vinetok synergistically inhibits DLBCL growth by downregulating the expression of MYC, BCL2 and TP53

Chinese summary:

Objective:

To investigate the effect of epigenetic histone deacetylase (HDAC) inhibitor sidabenamide with BCL2 inhibitor Venetok on the growth of diffuse large B-cell lymphoma (DLBCL) and related mechanisms
.

Innovations:

This study explores for the first time the combination of sidabenamide and vinetok on MYC⁺/BCL2⁺DLBCL, and uses second-generation sequencing (NGS) to pioneer the effects and mechanisms
of this combination from the epigenetic and gene protein levels.

Method:

Analysis of the correlation between the epigenetic HDAC gene and the BCL2 gene using bioinformatics techniques; DHL cell line DB (MYC/BCL2 rearrangement) and DEL cell line SUDHL-4 (MYC, BCL2 expression) were treated with single-agent and combination drug treatments respectively, cell viability was detected by CCK-8 method, apoptosis and cycle were detected by flow cytometry, and RNA sequencing and western blot (western blot) were used to detect mRNA levels and protein expression of MYC, BCL2, TP53 and other related genes.
In vivo, a mouse model of DLBCL xenograft was established for single-agent and combination drug therapy, and the size and pathological sections of the subcutaneous tumor after drug treatment were analyzed and evaluated
.

Conclusion:

Sidabenamide synergistically inhibits the growth of DLBCL by regulating epigenetic changes, silencing the expression of MYC and TP53, reducing the expression of anti-apoptotic protein BCL2 and increasing the BIM expression of pro-apoptotic protein, inducing apoptosis and cell cycle block
in tumor cells.

Keyword group:

Diffuse large B-cell lymphoma (DLBCL); MYC； BCL2； TP53； Venetock; Cidabenamide

Author:

Cancan LUO, Tiantian YU, Ken H.
YOUNG, Li YU

This article references format:

Cancan LUO, Tiantian YU, Ken H.
YOUNG, Li YU.
HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via downregulation of MYC, BCL2, and TP53 expression[J].
Journal of Zhejiang University Science B, 2022, 23(8): 666-681.
 

http://doi.
org/10.
1631/jzus.
B2200016

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