Mitochondrial induction as a potential radio-sensitizer in lung cancer cells - a short report

作者：Shavit Ronen; Ilouze Maya; Feinberg Tali; Lawrence Yaacov Richard; Tzur Yossi; Peled Nir^*

来源：Cellular Oncology, 2015, 38(3): 247-252.

DOI：10.1007/s13402-014-0212-6

• NSCLC
• DCA
• Mitochondria
• Radiation
• Radio-sensitizer
• Warburg effect

Lung cancer is the leading cause of cancer death. Radiation therapy plays a key role in its treatment. Ionizing radiation induces cell death through chromosomal aberrations, which trigger mitotic catastrophe and apoptosis. However, many lung cancer patients show resistance to radiation. Dichloroacetate (DCA) is a small molecule that can promote mitochondrial activation by increasing the influx of pyruvate. Here, we tested whether DCA may increase the sensitivity of non-small cell lung cancer (NSCLC) cells to radiation through this mechanism.
Two representative NSCLC cell lines (A549 and H1299) were tested for their sensitivity to radiation with and without pre-exposure to DCA. The treatment efficacy was evaluated using a clonogenic survival assay. An extracellular flux analyzer was used to assess the effect of DCA on cellular oxygen consumption as a surrogate marker for mitochondrial activity.
We found that DCA increases the oxygen consumption rate in both A549 and H1299 cells by 60 % (p = 0.0037) and 20 % (p = 0.0039), respectively. Pre-exposure to DCA one hour before radiation increased the cytotoxic death rate 4-fold in A549 cells (55 to 13 %, p = 0.004) and 2-fold in H1299 cells (35 to 17 %, p = 0.28) respectively, compared to radiation alone.
Mitochondrial induction by DCA may serve as a radio-sensitizer in non-small cell lung cancer.

• 出版日期2015-6