Autophagy has recently emerged as a significant mechanism in
cancer treatment. Although
gemcitabine and/or ionizing radiation are important modalities in the treatment of
pancreatic cancer, the contribution of autophagy in such treatment has not been fully elucidated. This study investigated the role of autophagy in the treatment of
pancreatic cancer with
gemcitabine and ionizing radiation. To evaluate the effect of
gemcitabine and/or ionizing radiation on autophagy, several human
pancreatic cancer cell lines were used. The treatment of
pancreatic cancer cell cultures in vitro and in vivo with
gemcitabine and ionizing radiation resulted in synergistic cytotoxicity.
After treatment with
gemcitabine, the
autophagy-related protein light chain 3-II (LC3-II) was upregulated. When
gemcitabine was combined with ionizing radiation treatment, LC3-II upregulation was enhanced. In addition, electron microscopy of
pancreatic cancer cells treated with
gemcitabine and/or ionizing radiation detected the induction of autophagy. The blockage of autophagy by
3-methyladenine indicated that autophagy contributed to cell death after
gemcitabine treatment and enhanced its cytotoxicity. The inhibitory effect and immune reactivity of the
autophagy-related proteins LC3 and
beclin-1 were the strongest after the combination treatment. In conclusion, these results suggest that autophagy can be activated by
gemcitabine and/or ionizing radiation in the treatment of
pancreatic cancer cells and that activated autophagy plays a role in
cancer suppression. These findings may have important implications for future therapeutic strategies using
gemcitabine and ionizing radiation against
pancreatic cancer.