Knockdown of Chitinase 3-Like-1 Inhibits Cell Proliferation, Promotes Apoptosis, and Enhances Effect of Anti-Programmed Death Ligand 1 (PD-L1) in Diffuse Large B Cell Lymphoma Cells
BACKGROUND Enzymatically inactive chitinase-like protein CHI3L1 is overexpressed in diffuse large B cell lymphoma (DLBCL) patients with PD-L1 imbalance and promotes tumor progression in the microenvironment. Based on this, we investigated how CHI3L1 acts on the proliferation and apoptosis of DLBCL and whether there is a synergy of CHI3L1 in combination with anti-PD-L1 antibodies in vivo. MATERIAL AND METHODS CHI3L1 was detected by quantitative real-time PCR (RT-PCR) and western blot (WB) in B-lymphoma cell lines. CHI3L1 interference plasmids were constructed, and the levels of proliferation, cell cycle, apoptosis, and cell survival were examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model by RT-PCR, WB, CCK-8, and flow cytometry. RESULTS CHI3L1 was significantly expressed in SU-DHL-4 cells. CHI3L1-interfered RNA ShRNA-CHI3L1-1 was chosen to be used in the next experiment because it had a better interference effect. Dampened cell proliferation level, arrested cell cycle, reduced protein expressions of cyclin D1 and cyclin D2, and promoted cell apoptosis level were observed after SU-DHL-4 was transfected with ShRNA-CHI3L1-1. Furthermore, we also noticed increased expression of Bcl-2, decreased expressions of bax, cleaved caspase 3 and cleaved PARP, promoted cell survival-related protein p53, and reduced survivin. CONCLUSIONS This study demonstrated that knockdown of CHI3L1 inhibits cancer cell proliferation by regulating cell cycles, promotes cancer cell apoptosis, and enhances the pro-apoptotic effect of anti-PD-L1 antibody both in vivo and in vitro in DLBCL.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Medical science monitor : international medical journal of experimental and clinical research - 27(2021) vom: 25. März, Seite e929431 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Xiao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.06.2021 Date Revised 01.06.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.12659/MSM.929431 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323209157 |
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| 100 | 1 | |a Yang, Xiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Knockdown of Chitinase 3-Like-1 Inhibits Cell Proliferation, Promotes Apoptosis, and Enhances Effect of Anti-Programmed Death Ligand 1 (PD-L1) in Diffuse Large B Cell Lymphoma Cells |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND Enzymatically inactive chitinase-like protein CHI3L1 is overexpressed in diffuse large B cell lymphoma (DLBCL) patients with PD-L1 imbalance and promotes tumor progression in the microenvironment. Based on this, we investigated how CHI3L1 acts on the proliferation and apoptosis of DLBCL and whether there is a synergy of CHI3L1 in combination with anti-PD-L1 antibodies in vivo. MATERIAL AND METHODS CHI3L1 was detected by quantitative real-time PCR (RT-PCR) and western blot (WB) in B-lymphoma cell lines. CHI3L1 interference plasmids were constructed, and the levels of proliferation, cell cycle, apoptosis, and cell survival were examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model by RT-PCR, WB, CCK-8, and flow cytometry. RESULTS CHI3L1 was significantly expressed in SU-DHL-4 cells. CHI3L1-interfered RNA ShRNA-CHI3L1-1 was chosen to be used in the next experiment because it had a better interference effect. Dampened cell proliferation level, arrested cell cycle, reduced protein expressions of cyclin D1 and cyclin D2, and promoted cell apoptosis level were observed after SU-DHL-4 was transfected with ShRNA-CHI3L1-1. Furthermore, we also noticed increased expression of Bcl-2, decreased expressions of bax, cleaved caspase 3 and cleaved PARP, promoted cell survival-related protein p53, and reduced survivin. CONCLUSIONS This study demonstrated that knockdown of CHI3L1 inhibits cancer cell proliferation by regulating cell cycles, promotes cancer cell apoptosis, and enhances the pro-apoptotic effect of anti-PD-L1 antibody both in vivo and in vitro in DLBCL | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Blocking |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a BCL2 protein, human |2 NLM | |
| 650 | 7 | |a CD274 protein, human |2 NLM | |
| 650 | 7 | |a CHI3L1 protein, human |2 NLM | |
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| 700 | 1 | |a Fang, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiayi |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Yuanbo |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Jianming |e verfasserin |4 aut | |
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