Development of novel application of 3,3 '-diindolylmethane: sensitizing multidrug resistance human breast cancer cells to gamma-irradiation

作者：Wang Wenjing; Lv Maomin; Wang Yanlin; Zhang Jingang^*

来源：Pharmaceutical Biology, 2016, 54(12): 3164-3168.

DOI：10.1080/13880209.2016.1192198

• Apoptosis
• breast carcinoma
• radio-sensitization

Context: Multidrug resistance (MDR) is known as a major obstacle to effective cancer therapy. The effects of irradiation on MDR in cancer cells had rarely been reported.
Objective: The effect of 3,3'-diindolylmethane (DIM) sensitizing MDR human breast carcinoma to gamma-irradiation was investigated.
Materials and methods: MCF-7/ADR cells were exposed to different concentrations of DIM (0-30 mu M) for 48 or 2 h before IR (gamma-Co-60, 10Gy, room temperature) then cultured for 48 h. Cell survival was determined by MTT assay. Intracellular reactive oxygen spices (ROS) induced by DIM (20 and 30 mu M, 2 h before irradiation) was measured by flow cytometry. Propidium iodide staining assay was used for cell cycle distribution studies; cell apoptosis was measured by flow cytometry and confocal microscopy.
Results: DIM (20 and 30 mu M, 2 h before irradiation) sensitized MCF-7/ADR cells to IR with survival rates decreased from 100% to 79% and 63%, respectively. DIM combined with gamma-radiation demonstrated that the activity of G2/M phase cell cycle arresting with percentages enhanced from 9% to 49% and 52%. DIM can increase intracellular ROS generation by 1.45- and 1.55-times compared to control group. Significantly enhanced radiation-induced apoptosis by DIM was also observed.
Discussion and conclusion: These data provide a rationale for the use of DIM as a promising radio-sensitizer to MDR cancer cells.

• 出版日期2016-12
• 单位中国人民解放军军事医学科学院