Mitochondrial DNA depletion induces radioresistance by suppressing G2 checkpoint activation in human pancreatic cancer cells.
Mitochondrial DNA depletion induces radioresistance by suppressing G2 checkpoint activation in human pancreatic cancer cells.
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DOI：
10.1667/rr1395.1
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发表时间：
2009-05
影响因子：
3.4
通讯作者：
Cullen JJ
中科院分区：
文献类型：
--
作者：
Cloos CR;Daniels DH;Kalen A;Matthews K;Du J;Goswami PC;Cullen JJ
We hypothesized that mitochondrial function regulates cell cycle checkpoint activation and radiosensitivity. Human pancreatic tumor cells (MiaPaCa-2, rho+) were depleted of mitochondrial DNA (rho°) by culturing cells in the presence of ethidium bromide. Depletion of mitochondrial DNA was verified by PCR amplification of total DNA using primer pairs specific for mitochondrial DNA. Loss of mitochondrial DNA decreased plating efficiency and the percentage of cells in S phase. Exponential cultures were irradiated with 2, 4 and 6 Gy (dose rate: 0.83 Gy/min) of ionizing radiation and harvested for determination of cell viability, growth and cell cycle phase distributions. Rho° cells were radioresistant compared to rho+ cells, with a dose-modifying factor (DMF) of 1.6. Although cell growth was significantly inhibited in irradiated rho+ cells compared to unirradiated control cells, the inhibition in Rho° cells was minimal. In addition, mitochondrial DNA depletion suppressed radiation-induced G2 checkpoint activation, which was accompanied by increases in both cyclin B1 and CDK1. These results suggest that mitochondrial function may regulate cell cycle checkpoint activation and radio-sensitivity in pancreatic cancer cells.
