Abstract 1670: Sensitization of non-small cell lung cancer cells (NSCLC) to radiation by Vitamin D (1,25-D3).
Authors: Khushboo Sharma
Journal: Cancer Research (2013)

Abstract Lung cancer is one of the leading causes of cancer related cell deaths in the United States and other industrialized countries, accounting for 40% of all cancer deaths in both men and women. Although smoking cessation programs have led to a decline in death rates, the need for improved therapies remains, as the mortality rates for lung cancer patients have not significantly changed over the years. Patients with non-small cell lung cancer (NSCL) have a poor prognosis and the median survival rate is less than 12 months. In previous studies, vitamin D (1,25-D3) and its analogue, EB 1089, have been shown to enhance anti-proliferative and anti -tumorogenic effects in breast tumor cells exposed to radiation. Our current research efforts were designed to study the effects of 1,25-D3 on the response to radiation in models of non-small cell lung cancer. Autophagy, a catabolic process which involves degradation of the cell's own components such as mitochondria and endoplasmic reticulum to generate energy under conditions of stress, has been shown to be the primary mode of radiosensitization by vitamin D in breast tumor cells. A549 non-small cell lung tumor cells, when treated with radiation alone, demonstrate a transient growth arrest followed by proliferative recovery, whereas a more prolonged growth arrest with minimal recovery is observed for the combination treatment of 1,25-D3 + radiation. Induction of autophagy by the combination treatment of 1,25-D3 + radiation was detected based on increased acridine orange staining, flow cytometric quantification of autophagic vesicles and RFP-LC3 redistribution. Induction of autophagic flux was evident based on degradation of p62. Other modes of cell death and growth arrest, specifically apoptosis and senescence, were also evaluated using flow cytometry and beta-galactosidase staining respectively. Minimal induction of both apoptosis and senescence indicated that autophagy induction maybe a primary mode of radio-sensitization in A549 lung tumor cells. 1,25-D3 failed to modify the extent of growth arrest or suppress proliferative recovery in H838 lung tumor cells, which lack the vitamin D receptor; similarly, there was no evidence of radiosensitization in normal human bronchial cells. These studies affirm the requirement of the vitamin D receptor for radiosensitization by vitamin D and also indicate that the combination treatment is selective in nature. Future studies will be directed towards identifying the signaling pathways mediating sensitization to radiation by vitamin D in non-small cell lung cancer. Citation Format: Khushboo Sharma. Sensitization of non-small cell lung cancer cells (NSCLC) to radiation by Vitamin D (1,25-D3). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1670. doi:10.1158/1538-7445.AM2013-1670 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.