In vitro assessment of the efficiency of the PIM-1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma

被引：4

作者：

Alsubaie, Mona ^{[1
,2
,3
]}

Matou-Nasri, Sabine ^{[1
,4
]}

Aljedai, Abdullah ^{[3
]}

Alaskar, Ahmed ^{[4
,5
,6
]}

Al-Eidi, Hamad ^{[1
]}

Albabtain, Sarah A. ^{[7
]}

Aldilaijan, Khawlah E. ^{[7
]}

Alsayegh, Manal ^{[1
]}

Alabdulkareem, Ibrahim B. ^{[1
,7
]}

机构：

[1] Minist Natl Guard Hlth Affairs, King Abdullah Int Med Res Ctr, Med Genom Res Dept, Cell & Gene Therapy Grp, POB 22490, Riyadh 11481, Saudi Arabia

[2] Prince Sattam Bin Abdulaziz Univ, Coll Appl Med Sci, Dept Lab Med Sci, Hematol & Serol Unit, Riyadh 11942, Saudi Arabia

[3] King Saud Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Riyadh 12372, Saudi Arabia

[4] King Saud Bin Abdulaziz Univ Hlth Sci, Coll Med, Riyadh 11481, Saudi Arabia

[5] Minist Natl Guard Hlth Affairs, King Abdullah Med City, Dept Oncol, Div Adult Hematol & Hematopoiet Stem Cell Transpl, Riyadh 14611, Saudi Arabia

[6] Minist Natl Guard Hlth Affairs, King Abdullah Int Med Res Ctr, Riyadh 11426, Saudi Arabia

[7] Princess Nourah Bint Abdulrahman Univ, Hlth Sci Res Ctr, Search Dept, Riyadh 11564, Saudi Arabia

来源：

ONCOLOGY LETTERS | 2021年 / 22卷 / 02期

关键词：

Burkitt's lymphoma; Daudi cells; Raji cells; proviral integration of the Moloney murine leukemia virus kinase; proviral integration of the Moloney murine leukemia virus pharmacological inhibitor; apoptosis; CANCER; SURVIVAL; APOPTOSIS; TARGET; MYC; PROTEIN; BAD;

D O I：

10.3892/ol.2021.12883

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Burkitt's lymphoma is an aggressive form of lymphoma affecting B lymphocytes. It occurs endemically in Africa and sporadically in the rest of the world. Due to the high proliferation rate of this tumor, intensive multi-drug treatment is required; however, the risk of tumor syndrome lysis is high. Overexpression of the proto-oncogene proviral integration of the Moloney murine leukemia virus (PIM-1) kinase is associated with the development of hematological abnormalities, including Burkitt's lymphoma (BL). PIM-1 primarily exerts anti-apoptotic activities through BAD phosphorylation. The aim of the present study was to investigate the in vitro efficiency of a PIM-1 kinase pharmacological inhibitor (PIM1-1) in BL. The impact of PIM1-1 was evaluated in terms of the viability and apoptosis status of the BL B cell lines, Raji and Daudi, compared with K562 leukemia cells, which highly express PIM-1. Cell viability and apoptotic status were assessed with western blotting, and PIM-1 gene expression was assessed with reverse transcription-quantitative PCR. After 48 h of treatment, PIM1-1 inhibited the Daudi, Raji and K562 cell viability with a half-maximal inhibitory concentration corresponding to 10, 20 and 30 mu M PIM1-1, respectively. A significant decrease of ERK phosphorylation was detected in PIM1-1-treated Daudi cells, confirming the antiproliferative effect. The addition of 10 mu M PIM1-1 significantly decreased the PIM-1 protein and gene expression in Daudi cells. An inhibition of the pro-apoptotic BAD phosphorylation was observed in the Daudi cells treated with 0.1-1 mu M PIM1-1 and 10 mu M PIM1-1 decreased BAD phosphorylation in the Raji cells. The apoptotic status of both PIM1-1-treated cells lines were confirmed with the detection of cleaved capase-3. However, no change in cell viability and PIM-1 protein expression was observed in the 10 mu M PIM1-1-treated K562 cells. In conclusion, the findings indicated that the PIM1-1 pharmacological inhibitor may have therapeutic potential in BL, but with lower efficiency in leukemia.

引用

页数：8

共 38 条

[1] Pim-1 kinase promotes inactivation of the pro-apoptotic bad protein by phosphorylating it on the Ser112 gatekeeper site [J].