The effect of the ATM inhibitor AZD0156 on the radiosensitivity of human breast cancer and lung fibroblast cells

Aims: To evaluate the effect of the combination of irradiation and AZD0156 on apoptosis, cell cycle progression, and clonogenic survival in human breast cancer and fibroblast cells.

Methods and material: Estrogen receptor-positive breast cancer cell line MCF-7 and healthy lung fibroblast cell line WI-38 were obtained. Following employing proliferation analysis, cytotoxicity analysis was done to calculate the IC50 values of AZD0156 in MCF-7 and WI-38 cell lines. Following the application of AZD0156 and irradiation, flow cytometry analysis was performed for evaluating cell cycle distribution and the extent of apoptosis. Plating efficiency and surviving fraction were calculated for the clonogenic assay.

Statistical analysis used: SPSS Statistics for Windows, Version 17.0. (SPSS Inc. Chicago) and GraphPad Prism Version 6.0 for Windows (GraphPad Software, San Diego, California USA) softwares were used to analyze data.

Results: AZD0156 and irradiation dose of 2-10 Gy had no effect on apoptosis on MCF-7 cells. The combination treatment of AZD0156 and 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy irradiation induced G0/G1 phase arrest by 1.79, 1.79, 1.50, 1.25, and 1.52-fold compared to the control group, respectively on MCF-7 cell lines. Combination treatment of AZD0156 and each different irradiation dose affected clonogenic survival owing to increased radiosensitivity (p: 0.02). AZD0156 and irradiation dose of 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy decreased the cell viability rate of WI-38 cells by 1.05, 1.18, 1.22, 1.04, and 1.05-fold compared to the control group, respectively. No efficacy was detected on cell cycle analysis, and clonogenic survival was not significantly decreased in WI-38 cells.

Conclusion: The combination use of irradiation and AZD0156 has improved efficacy of tumor cell-specific cell cycle arrest and decreasing clonogenic survival.

 

Comments:

The aim of this study was to evaluate the effects of combining irradiation and AZD0156 on apoptosis, cell cycle progression, and clonogenic survival in human breast cancer (MCF-7) and fibroblast (WI-38) cells.

The researchers first obtained the MCF-7 breast cancer cell line and WI-38 lung fibroblast cell line. They performed proliferation analysis and cytotoxicity analysis to determine the IC50 values of AZD0156 in both cell lines.

After determining the appropriate doses of AZD0156 and irradiation, the researchers conducted flow cytometry analysis to assess the cell cycle distribution and extent of apoptosis. They also calculated the plating efficiency and surviving fraction in a clonogenic assay.

The statistical analysis was performed using SPSS Statistics and GraphPad Prism software.

The results showed that AZD0156 and irradiation doses of 2-10 Gy had no effect on apoptosis in MCF-7 cells. However, the combination treatment of AZD0156 with irradiation at doses of 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy induced G0/G1 phase arrest by 1.79, 1.79, 1.50, 1.25, and 1.52-fold, respectively, compared to the control group in MCF-7 cells. The combination treatment also increased radiosensitivity and affected clonogenic survival in MCF-7 cells.

In WI-38 cells, AZD0156 and irradiation doses of 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy decreased cell viability rates by 1.05, 1.18, 1.22, 1.04, and 1.05-fold, respectively, compared to the control group. However, no significant effects were observed in cell cycle analysis and clonogenic survival in WI-38 cells.

In conclusion, the combination treatment of irradiation and AZD0156 showed improved efficacy in inducing tumor cell-specific cell cycle arrest and decreasing clonogenic survival in breast cancer cells (MCF-7). However, no significant effects were observed in fibroblast cells (WI-38).

Related Products

Cat.No.	Product Name	Information
S8375	AZD0156	AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities. AZD0156 prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells.

Related Targets

ATM/ATR Apoptosis related