3-bromopyruvic acid inhibits the proliferation of malignant transformed dendritic cells

Objective To explore the possible inhibiting effect of 3-bromopyruvic acid (3-BrPA) on proliferation of malignant transformed dendritic cells by blocking the pathway of glucose metabolism. Methods In vitro, co-cultured mice myeloid dendritic cells (DC) with human glioma stem cells (SU3) were used to induce the malignant transformation of DC. Among DC monoclonal for malignant transformation, i. e., glioma stem/progenitor cells induced by malignant transformation of dendritic cells (GSPC-MTDCs), proliferative abilities of SU3, normal DC and GSPC-MTDCs were detected by CCK-8 and flat clone formation assay. Cell invasiveness was detected by Transwell chamber invasion assay. Subcutaneous inoculation of GSPC-MTDCs was performed in 20 non-fluorescent nude mice. At 11 d post inoculation, 10 nude mice with uniform tumorigenesis were divided into intervention group and control group with 5 mice in each group. The intervention group was given 3-BrPA (5 mg·kg-1·d-1) intraperitoneal treatment, while the control group was given the same volume of normal saline. After 24 days of intervention, the tumorigenesis was compared between 2 groups. Results (1) GSPC-MTDCs had immortalized characteristics. Compared with SU3, the proliferation rate of GSPC-MTDCs was faster and the clone formation rate was significantly higher (38.1±1.9% vs. 30.2±2.7%, P<0.01). Transwell chamber invasion test showed that GSPC-MTDCs had stronger invasive ability than SU3 (1 042±49 vs. 782±38, P<0.01). (2) GSPC-MTDCs inoculated into the subcutaneous and caudal veins of non-fluorescent nude mice all formed tumors. At 24 days after 3-BrPA intervention, the tumor masses in the intervention group and the control group were 1.5±0.6 g and 3.3±1.0 g, respectively. The difference was statistically significant (P=0.0107). Pathological observation showed that compared with the intervention group, the control group had more abnormal nuclei, more mitosis, abundant blood vessels, obvious infiltration of inflammatory cells and higher proportion of c-myc positive cells. Conclusions Glioma stem cells have the potential to induce malignant transformation of DC cells. 3-BrPA could inhibit the proliferation of GSPC-MTDCs. Key words: Glioma; Dendritic cells; Neoplasm transplantation; Cell proliferation; 3-bromopyruvic acid; Tumor suppressor; Mice