BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling
Objective: Follicular lymphoma (FL) is an indolent B-cell lymphoproliferative disorder, characterized by a lymphoid follicular pattern of growth. PFI-1 or CPI-203 has been known to effectively promote the inhibition of primary effusion lymphoma progression. This study aimed at investigating the anti...
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024031803 |
| _version_ | 1797259822481014784 |
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| author | Min Bai Yunpeng Huang Xinrui Suo Lieyang Wang Weie Han Weihua Zhang |
| author_facet | Min Bai Yunpeng Huang Xinrui Suo Lieyang Wang Weie Han Weihua Zhang |
| author_sort | Min Bai |
| collection | DOAJ |
| description | Objective: Follicular lymphoma (FL) is an indolent B-cell lymphoproliferative disorder, characterized by a lymphoid follicular pattern of growth. PFI-1 or CPI-203 has been known to effectively promote the inhibition of primary effusion lymphoma progression. This study aimed at investigating the anti-tumor properties of PFI-1 and CPI-203 on FL cells and uncover the underlying mechanism of action. Methods: FL cells were treated with PFI-1 and CPI-203, and the treated cells were evaluated for their cell viability, cell cycle and apoptosis using CCK8, flow cytometry, and Western blot assays. A xenograft mouse model was used for assessing the in vivo effects of CPI-203 on tumorigenesis. Results: PFI-1 or CPI-203 showed potential inhibitory effects on the cell viability of DOHH2 and RL cells in a dose-response-dependent manner. Furthermore, PFI-1 and CPI-203 inhibited cell growth, induced apoptosis of FL cells in vitro, and facilitated the translocation of β-catenin into cytoplasm both in vitro and in vivo. After engrafted with FL cells, CPI-203-treated mice got a longer duration of survival and a smaller tumor size than control mice. Mechanistically, PFI-1 and CPI-203 impede the activity of β-catenin and its downstream molecules by regulating the DVL2/GSK3β axis. Conclusion: In conclusion, PFI-1 and CPI-203 may serve as potential anti-tumor inhibitors for the therapy of FL. |
| first_indexed | 2024-03-07T16:53:30Z |
| format | Article |
| id | doaj.art-e4367840b5f840299345cbb2816d3207 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:15:32Z |
| publishDate | 2024-03-01 |
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| series | Heliyon |
| spelling | doaj.art-e4367840b5f840299345cbb2816d32072024-03-17T07:57:29ZengElsevierHeliyon2405-84402024-03-01105e27149BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signalingMin Bai0Yunpeng Huang1Xinrui Suo2Lieyang Wang3Weie Han4Weihua Zhang5Hematology department, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, ChinaHematology department, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, ChinaDepartment of Prevention and Health, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, ChinaHematology department, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, ChinaHematology department, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, ChinaHematology Department, The First Hospital, Shanxi Medical University, Taiyuan, 030001, China; Corresponding author. Hematology department, The First Hospital, Shanxi Medical University, 85 Jiefang South Road, Taiyuan, China.Objective: Follicular lymphoma (FL) is an indolent B-cell lymphoproliferative disorder, characterized by a lymphoid follicular pattern of growth. PFI-1 or CPI-203 has been known to effectively promote the inhibition of primary effusion lymphoma progression. This study aimed at investigating the anti-tumor properties of PFI-1 and CPI-203 on FL cells and uncover the underlying mechanism of action. Methods: FL cells were treated with PFI-1 and CPI-203, and the treated cells were evaluated for their cell viability, cell cycle and apoptosis using CCK8, flow cytometry, and Western blot assays. A xenograft mouse model was used for assessing the in vivo effects of CPI-203 on tumorigenesis. Results: PFI-1 or CPI-203 showed potential inhibitory effects on the cell viability of DOHH2 and RL cells in a dose-response-dependent manner. Furthermore, PFI-1 and CPI-203 inhibited cell growth, induced apoptosis of FL cells in vitro, and facilitated the translocation of β-catenin into cytoplasm both in vitro and in vivo. After engrafted with FL cells, CPI-203-treated mice got a longer duration of survival and a smaller tumor size than control mice. Mechanistically, PFI-1 and CPI-203 impede the activity of β-catenin and its downstream molecules by regulating the DVL2/GSK3β axis. Conclusion: In conclusion, PFI-1 and CPI-203 may serve as potential anti-tumor inhibitors for the therapy of FL.http://www.sciencedirect.com/science/article/pii/S2405844024031803PFI-1CPI-203Follicular lymphomaCell growthApoptosisWnt/ β-catenin signaling pathway |
| spellingShingle | Min Bai Yunpeng Huang Xinrui Suo Lieyang Wang Weie Han Weihua Zhang BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling Heliyon PFI-1 CPI-203 Follicular lymphoma Cell growth Apoptosis Wnt/ β-catenin signaling pathway |
| title | BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling |
| title_full | BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling |
| title_fullStr | BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling |
| title_full_unstemmed | BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling |
| title_short | BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/β-catenin signaling |
| title_sort | bet bromodomain inhibitors pfi 1 and cpi 203 suppress the development of follicular lymphoma via regulating wnt β catenin signaling |
| topic | PFI-1 CPI-203 Follicular lymphoma Cell growth Apoptosis Wnt/ β-catenin signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024031803 |
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