@misc{oai:repo.qst.go.jp:00076615,
 author = {Suzuki, Motofumi and Ken-ichiro, Matsumoto and Nakanishi, Ikuo and Hasegawa, Sumitaka and Suzuki, Motofumi and Matsumoto, Kenichiro and Nakanishi, Ikuo and Hasegawa, Sumitaka},
 month = {Aug},
 note = {In eukaryotes, genotoxic stress such as chemotherapy and radiotherapy trigger autophagy. Basically, autophagy is known as a protective mechanism that facilitates the degradation of damaged cellular components. In addition, it has a role to maintain genome stability by regulating cell cycle. Similarly, cell-cycle checkpoints are mechanism that monitor the order, integrity, and fidelity of the major events of the cell cycle to sustain genome integrity. While both mechanisms have similar roles and function, the molecular mechanisms linking them together are still debated and largely unknown. In this study, we thus sought to elucidate the relationship between autophagy and cell-cycle checkpoint.
We first evaluated whether X-irradiation trigger autophagy by monitoring some autophagy markers such as LC3 and p62 in two pancreatic cancer cell lines, MIA PaCa-2 and SUIT-2, using immunoblotting and immunofluorescence. When pancreatic cancer cells were X-irradiated with 6 Gy, it triggered autophagy and peaked at 12 h after irradiation. In addition, we found that X-irradiation with 6 Gy induced G2/M accumulation at the same time point using immunoblotting and flowcytometric analysis. Furthermore, both events were attenuated by two G2 checkpoint inhibitors, MK-8776 (Chk1 inhibitor) or MK-1775 (Wee1 inhibitor). In a clonogenic survival assay, both G2 checkpoint inhibitors demonstrated a more pronounced radiosensitizing effect than an autophagy inhibitor, hydroxychloroquine.
Our data suggest that there may be interplay between radiation-induced autophagy and cell-cycle arrest via checkpoint activation, and this autophagy at least partly contributes to radioresistance via G2 checkpoint., 16th International Congress of Radiation Research (ICRR2019)},
 title = {The crosstalk between radiation-induced autophagy and G2 checkpoint and its application for radiotherapy in pancreatic cancer},
 year = {2019}
}