Article: [Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells].
Zhongguo shi yan xue ye xue za zhi
2022 Volume 30, Issue 1, Page(s) 175–182
Abstract: Objective: To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of ... ...
Abstract | Objective: To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. Methods: CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. Results: Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). Conclusion: Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells. |
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MeSH term(s) | Apoptosis ; Bortezomib/pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Interleukin-1 Receptor-Associated Kinases ; Multiple Myeloma ; Pentacyclic Triterpenes ; Signal Transduction |
Chemical Substances | Pentacyclic Triterpenes ; Bortezomib (69G8BD63PP) ; IRAK4 protein, human (EC 2.7.11.1) ; Interleukin-1 Receptor-Associated Kinases (EC 2.7.11.1) ; celastrol (L8GG98663L) |
Language | Chinese |
Publishing date | 2022-02-05 |
Publishing country | China |
Document type | Journal Article |
ZDB-ID | 2404306-0 |
ISSN | 1009-2137 |
ISSN | 1009-2137 |
DOI | 10.19746/j.cnki.issn.1009-2137.2022.01.029 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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