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Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells

View Article: PubMed Central - PubMed

ABSTRACT

Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co-stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co-stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- γ against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell-mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies.

No MeSH data available.


Related in: MedlinePlus

Effects of decitabine on tumor cell viability.Cells were seeded at an initial density of 1 × 105 cells/well in 6-well tissue culture plates and incubated for 24 h then treated with various concentrations of decitabine for 24 h. Cell viability was evaluated using an MTT assay. Results are expressed as percentage of the vehicle treated control ± standard deviation (SD) of three separate experiments. Statistical significance was determined using a Student’s t-test. #P < 0.05 (#untreated control versus decitabine).
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f1: Effects of decitabine on tumor cell viability.Cells were seeded at an initial density of 1 × 105 cells/well in 6-well tissue culture plates and incubated for 24 h then treated with various concentrations of decitabine for 24 h. Cell viability was evaluated using an MTT assay. Results are expressed as percentage of the vehicle treated control ± standard deviation (SD) of three separate experiments. Statistical significance was determined using a Student’s t-test. #P < 0.05 (#untreated control versus decitabine).

Mentions: To determine decitabine’s effects on tumor cell viability, an MTT assay was performed 24 h after decitabine treatment (0–10 μM). Treatment with decitabine at a concentration of 0–5 μM caused no cytotoxicity in tumor cell lines; however, the highest decitabine concentration tested (10 μM) resulted in approximately 20% inhibition of cell growth compared with that in controls in A549 cells (Fig. 1). Therefore, we used decitabine at a concentration of 5 μM for all remaining experiments, including studies of immunogenicity and tumor susceptibility to NK and T cells in various tumor cell lines.


Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells
Effects of decitabine on tumor cell viability.Cells were seeded at an initial density of 1 × 105 cells/well in 6-well tissue culture plates and incubated for 24 h then treated with various concentrations of decitabine for 24 h. Cell viability was evaluated using an MTT assay. Results are expressed as percentage of the vehicle treated control ± standard deviation (SD) of three separate experiments. Statistical significance was determined using a Student’s t-test. #P < 0.05 (#untreated control versus decitabine).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037374&req=5

f1: Effects of decitabine on tumor cell viability.Cells were seeded at an initial density of 1 × 105 cells/well in 6-well tissue culture plates and incubated for 24 h then treated with various concentrations of decitabine for 24 h. Cell viability was evaluated using an MTT assay. Results are expressed as percentage of the vehicle treated control ± standard deviation (SD) of three separate experiments. Statistical significance was determined using a Student’s t-test. #P < 0.05 (#untreated control versus decitabine).
Mentions: To determine decitabine’s effects on tumor cell viability, an MTT assay was performed 24 h after decitabine treatment (0–10 μM). Treatment with decitabine at a concentration of 0–5 μM caused no cytotoxicity in tumor cell lines; however, the highest decitabine concentration tested (10 μM) resulted in approximately 20% inhibition of cell growth compared with that in controls in A549 cells (Fig. 1). Therefore, we used decitabine at a concentration of 5 μM for all remaining experiments, including studies of immunogenicity and tumor susceptibility to NK and T cells in various tumor cell lines.

View Article: PubMed Central - PubMed

ABSTRACT

Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co-stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co-stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- &gamma; against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell-mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies.

No MeSH data available.


Related in: MedlinePlus