Low-Dose Decitabine-Based Chemoimmunotherapy for Patients with Refractory Advanced Solid Tumors: A Phase I/II Report
Figure 5
In vivo and in vitro biological activities of decitabine (DAC) were shown in human hepatocellular carcinoma HepG2 cell line and peripheral blood mononuclear cells (PBMCs). (a) Quantitative RT-PCR analyses of the mRNA levels of RASSF1A, MAGEA-3, MAGEA-1, p16, p15, and BRCA1 expression on human hepatocellular carcinoma HepG2 cell line; the cell lines were treated with 10 nM DAC for 72 h before collecting mRNA for analysis. Compared to untreated control, the mRNA expression levels of MAGEA-3, MAGEA-1, p16, and p15 were augmented significantly in treated cell line. (b, c) Quantitative RT-PCR analyses of the mRNA levels of MAGEA-3, MAGEA-1, p16, and p15 expression in peripheral blood mononuclear cells (PBMCs) from patients who exhibited prolonged disease stabilization following low-dose DAC treatment for the first cycle. Progressive increases in the mRNA expressions of MAGEA-3, MAGEA-1, p16, and p15 were observed in patient UNP 25; in contrast, the p16 and p15 mRNA expressions were reduced in patient UNP 14. (d) Methylation-specific PCR analyses of the changes in MAGEA-1 promoter methylation levels in peripheral blood mononuclear cells (PBMCs) collected from patients UNP 25 and UNP 14, during the first treatment cycle. The levels of MAGEA-1 promoter methylation of patients UNP 14 and UNP 25 were reduced and the levels of MAGEA-1 promoter unmethylation were increased at the same time. M: methylation; U: unmethylation. , for the significance of the gene expressions differences between the DAC treatment sample and the pre-DAC sample. Error bars represent standard deviation of the measurements.
