Evaluation of Radiation Response and Gold Nanoparticle Enhancement in Drug-Resistant Pancreatic Cancer Cells

Pancreatic cancer is a major cause of cancer-related death worldwide after lung cancer and colorectal cancer Pancreatic treatment modalities consist of surgery, chemotherapy, and radiation therapy or combination of these therapies. These modalities are good to some extents but they do have some limitations. For example, during the chemotherapy, tumor cells can develop some escape mechanisms and become chemoresistant to protect themselves against the chemo drugs and pass on theses escape mechanisms to their offspring, despite the treatment given. Cancer Cells can become chemoresistant by many mechanisms, for example, decreased drug influx mechanisms, decreased of drug transport molecules, decreased drug activation, altered drug metabolism that diminishes the capacity of cytotoxic drugs, and enhanced repair of DNA damage. Given that some of these chemoresistance mechanisms may impact sensitivity to radiation. Therefore, there is a strong need for a new alternative treatment option to amplify the therapeutic efficacy of radiotherapy and eventually increase the overall efficacy of cancer treatment. Nano-radiation therapy is an emerging and promising modality aims to enhance the therapeutic efficacy of radiotherapy through the use of radiosensitizing nanoparticles. The primary goal of using GNP-enhanced radiation is that GNPs are potent radiosensitizer agents that sensitize the tumor cells to radiation, and these agents promote generation of the free radicals produced by Photo- and Auger- electrons emission at the molecular level which can enhance the effectiveness of radiation-induced cancer cell death. The main aim of this research is to analyze and compare the response to radiation of pancreatic cancer cells, PANC-1, and PANC-1 cells that are resistant to oxaliplatin, PANC-1/OR, and investigate the radiation dose enhancement effect attributable to GNP when irradiating the cells with low-energy (220 kVp) beam at various doses. Based on evidence from the existing literature, we hypothesize that oxaliplatin-resistant pancreatic cancer cells, PANC-1/OR, are much more resistant to radiation exposure than their drug-sensitive analogues, PANC-1 cells. We think that the acquisition of chemoresistance entails mechanisms that also impart some loss of radiation sensitivity in PANC-1/OR cells. Responsiveness of pancreatic cancer cells to the radiation was measured by clonogenic survival. The results presented in this thesis show that drug-resistant PANC- 1/OR cells survive high doses of radiation exposure better than PANC-1 cells. Moreover, the presence of gold nanoparticles decreases cell survival when combined with the X-ray radiation. In conclusion, the combination of GNP and X-rays radiation produces a slight radiosensitizing effect for pancreatic cancer cells, PANC-1, and their chemoresistance variant, and we can speculate that this is a good mean of achieving additive cytotoxic effects on pancreatic cells