Article ; Online: Transcriptome Profiling Analysis Identifies LCP1 as a Contributor for Chidamide Resistance in Gastric Cancer.
2022 Volume 39, Issue 5, Page(s) 867–876
Abstract: Background: Gastric cancer (GC) remains a significant health problem and carries with it substantial morbidity and mortality. Chidamide is a novel and orally administered histone deacetylase (HDAC) inhibitor and has been demonstrated its anti-tumor ... ...
| Abstract | Background: Gastric cancer (GC) remains a significant health problem and carries with it substantial morbidity and mortality. Chidamide is a novel and orally administered histone deacetylase (HDAC) inhibitor and has been demonstrated its anti-tumor efficacy on different kinds of hematological and solid tumors. However, the underlying mechanism of chidamide resistance is still poorly characterized. Methods: We established chidamide resistant GC cell lines, AGS ChiR and MGC803 ChiR and investigated the toxicologic effects through cell survival, colony formation and flow cytometry assays in vitro, and a subcutaneous xenograft model in vivo. RNA-sequence was then performed to screen chidamide resistance-associated genes between AGS and AGS ChiR cells. The role of Lymphocyte cytosolic protein 1 (LCP1) in chidamide resistance was explored by gain- and loss-of-function analyses. Results: We found that chidamide significantly inhibited cell proliferation and induced the apoptosis in a concentration-dependent manner in wild-type GC cell lines as compared to chidamide resistant cell lines. The transcriptomic profiling, quantitative RT-PCR, and western blot data revealed that LCP1 was upregulated in AGS ChiR cells compared with parental cells. Overexpression of LCP1 conferred and knockdown of LCP1 attenuated the chidamide resistance of GC cells. Epigenetic derepression of LCP1 by chidamide may be a possible reason for the contribution of LCP1 to chidamide resistance. Conclusions: These findings illustrated that LCP1 may play a chidamide resistance role in GC, suggesting that LCP1 could be a potential target for the therapy of GC combined with chidamide. |
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| MeSH term(s) | Aminopyridines/pharmacology ; Apoptosis ; Benzamides/pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm/genetics ; Gene Expression Profiling ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Microfilament Proteins/genetics ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics |
| Chemical Substances | Aminopyridines ; Benzamides ; Histone Deacetylase Inhibitors ; LCP1 protein, human ; Microfilament Proteins ; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide (87CIC980Y0) |
| Language | English |
| Publishing date | 2022-05-16 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 843063-9 |
| ISSN | 1573-904X ; 0724-8741 ; 0739-0742 |
| ISSN (online) | 1573-904X |
| ISSN | 0724-8741 ; 0739-0742 |
| DOI | 10.1007/s11095-022-03291-1 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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