Relationship between the Release of Interleukin 12 and the Expression of PCNA, Cyclin A2, and CDK2 in Lung Cancer Cells

Objective: Mesenchymal stem cell (MSC)-based IL-12 release therapy may be less toxic than direct administration of IL-2.We investigated the release of interleukin (IL)-12 in MSCs and A549 cocultures and identified the time points at which IL-12 is secreted.We also examined changes in the expression of proliferative genes, such as proliferating cell nuclear antigen (PCNA), cyclin A2, and cyclin-dependent kinase 2 (CDK2). Material and Methods:This study was conducted by culturing A549 cells, MSCs, and MSC-A549 cells at 3 different time points.The release of IL-12p70 from cells in the collected culture media was determined by Enzyme-Linked ImmunoSorbent Assay.The expression of the PCNA, cyclin A2, and CDK2 genes involved in the cell cycle was determined quantitatively by reverse transcriptase polymerase chain reaction. Results:The expression of PCNA was the lowest, and the expression of the cyclin A2 and CDK2 genes was the highest in cocultured A549 cells, whereas the expression of the IL-12 protein was the highest at the 12 th h of coculture.The expression levels of the cyclin A2 and CDK2 genes decreased in cocultured A549 cells at the 24 th h in the presence of released IL-12.However, in A549 cells cultured alone, when the IL-12 level was the highest at the 24 th h, the cyclin A2 and CDK2 expression levels were high compared to those in the control group. Conclusion:IL-12 protein affects cell cycle regulatory genes, slows down cell proliferation, and may affect the prognosis of patients with this disease.