Abstract:
Aim of Study:To examine the function of lenalidomide (LEN) on the human multidrug resistance (MDR)-type gastric cancer line SGC7901/vincristine (VCR) via regulating Notch signaling. Materials and Methods:Quantitative polymerase chain reaction was used for checking the genes of Notch, DNA methyltransferase (DNMT), RBP-J, Hes1/5, Deltex1, MDR/multidrug resistant protein (MRP); the cell proliferation and cell death were detected by cell counting kit-8 (CCK8) staining, Ki-67 expression, and propidium-iodide staining, and methylated DNA immunoprecipitation assay (MeDIP) was used for checking the 5 mC enrichment, indicating the DNA methylation of the Notch2 gene loci. Results:LEN reduced the mRNA expression of Notch2 (P < 0.01) and increased the expression of the DNMT3A (P < 0.001) in SGC7901/VCR cell, suggesting the involvement of epigenetic regulation by DNMT3A on Notch2 gene expression. Consistently, Notch2 gene expression showed no obvious change between the LEN treatment and the control when the DNMT3A was knockdown using the interference of shRNA. The modulation of DNA methylation process on gene expression was then confirmed by 5 mC enrichment on Notch2 gene loci after LEN treatment. Furthermore, LEN could suppress the downstream genes in Notch2 signaling including RBP-J (P < 0.05), Hes1 (P < 0.001), and Deltex1 (P < 0.01). Due to the changes of gene expression pattern in Notch pathway, LEN showed a phenotype of cell proliferation suppression using CCK8 staining. Meanwhile, the expression of the genes associated with MDR and MRP was also significantly decreased (MDR, P < 0.01; MRP, P < 0.001) after LEN treatment. Therefore, inhibition of cell proliferation by LEN via Notch2 signaling combined with the MDR/MRP expression modulation contributes to the efficacy of LEN on the gastric cancer cell line SGC7901/VCR. Conclusion:The data implicate that LEN would be an effective chemical for the therapy of drug-resistant human gastric cancer cell and the gastric cancer patients.
journal_name
J Cancer Res Therjournal_title
Journal of cancer research and therapeuticsauthors
Ding W,Zeng T,Tao W,Ge W,Deng J,Lei H,Xiao Y,Liao Fdoi
10.4103/0973-1482.183181subject
Has Abstractpub_date
2018-01-01 00:00:00pages
S237-S242issue
Supplementeissn
0973-1482issn
1998-4138pii
JCanResTher_2018_14_8_237_183181journal_volume
14pub_type
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journal_title:Journal of cancer research and therapeutics
pub_type: 杂志文章
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journal_title:Journal of cancer research and therapeutics
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journal_title:Journal of cancer research and therapeutics
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journal_title:Journal of cancer research and therapeutics
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journal_title:Journal of cancer research and therapeutics
pub_type: 杂志文章,meta分析
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journal_title:Journal of cancer research and therapeutics
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journal_title:Journal of cancer research and therapeutics
pub_type: 信件,评审
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更新日期:2013-01-01 00:00:00
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journal_title:Journal of cancer research and therapeutics
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journal_title:Journal of cancer research and therapeutics
pub_type: 已发布勘误
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更新日期:2016-07-01 00:00:00
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journal_title:Journal of cancer research and therapeutics
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doi:10.4103/0973-1482.150420
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journal_title:Journal of cancer research and therapeutics
pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章
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journal_title:Journal of cancer research and therapeutics
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journal_title:Journal of cancer research and therapeutics
pub_type: 杂志文章
doi:10.4103/0973-1482.200607
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journal_title:Journal of cancer research and therapeutics
pub_type: 杂志文章
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journal_title:Journal of cancer research and therapeutics
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pub_type: 杂志文章
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