Objectives: NSC631570 is a cytotoxic drug with the ability to be selectively accumulated in tumor tissue and activate apoptosis only in malignant cells and not in normal cells. Therapy with NSC631570 is accompanied by the stimulation of anticancer immune responses. It is known that cytotoxic anticancer drugs have additional effects on the immune system of tumor-bearing organism by increasing the immunogenic properties of tumor cells. This study aimed to investigate the immunogenicity of melanoma B16 after treatment with NSC631570.
Methods: Two melanoma B16 sublines with different metastatic potentials were used. For in vivo growth cells were inoculated intravenously into C57BL/6 mice. The anticancer effect was calculated according to the growth inhibition index. Cell viability was determined by the MTT test. Cell apoptosis and necrosis were assessed by flow cytometry. HMGB1 expression, the serum level of cytokines and cytokine profile in tumor tissue were determined by ELISA. TAP1 and TAP2 expression was evaluated in RT-PCR and by Western blot.
Results: Treatment of melanoma B16 cells with NSC631570 at apoptogenic concentrations induced tumor cell death accompanied by dose-dependent HMGB1 release in vitro. At the non-apoptogenic concentration the preparation caused an increase in TAP expression. The therapeutic efficacy of NSC631570 was also associated with strong release of HMGB1 in the serum of tumor-bearing mice and was more expressed in the case of the high-metastatic tumor variant. The therapeutic effect was accompanied by an increase of levels of Th1 cytokines in the serum and in tumor tissue of treated animals.
Conclusion: In addition to the direct induction of tumor cell apoptosis, the preparation can increase the tumor immunogenicity.
Antineoplastic drug; Immunogenicity; NSC631570; Tumor cell death
Advancing Our Understanding of Brain Disorders: Research Using Postmortem Brain Tissue.
Curtis MA, Vedam-Mai V
Methods in molecular biology (Clifton, N.J.). 2022; 2389(): 201-208
Highly sensitive detection of multiple proteins from single cells by MoS-FET biosensors.
Wei J, Zhao Z, Lan K, Wang Z, Qin G, Chen R
Talanta. 2022; 236(): 122839
Identifying Neural Progenitor Cells in the Adult Human Brain.
Park TIH, Waldvogel HJ, Montgomery JM, Mee EW, Bergin PS, Faull RLM, Dragunow M, Curtis MA
Methods in molecular biology (Clifton, N.J.). 2022; 2389(): 125-154
Isolation and Enrichment of Defined Neural Cell Populations from Heterogeneous Neural Stem Cell Progeny.
Methods in molecular biology (Clifton, N.J.). 2022; 2389(): 111-123
Improving cell transplantation by understanding and manipulating the phagocytic activity of peripheral glia.
Nazareth L, St John J, Ekberg J
Neural regeneration research. 2022; 17(2): 313-314