Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells.
Bottom Line: Heavy-ion radiotherapy has a potential advantage over conventional radiotherapy due to improved dose distribution and a higher biological effectiveness in cancer therapy.The ability of carbon ions to inhibit the activation of the PI3K/Akt pathway rose with increasing their LET.Our data imply that targeting autophagy might enhance the effectiveness of heavy-ion radiotherapy.
Affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China.Show MeSH
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Mentions: First, the autophagic effect induced by the carbon ions with LET of 75 keV/μm in tumor cells was observed at the morphologic level. The MDC dye was used to assess levels of mature autophagic vesicle formation in HeLa cells following irradiation. Unirradiated cells (control) showed diffusive MDC staining instead of a punctate staining pattern. In contrast, the irradiated cells showed extensive punctate staining of bright blue, as shown in the Figure 1(a). Figure 1(b) shows that the redistribution of GFP-LC3 from a diffusive cytosolic to a punctate autophagosome associated pattern was observed in HeLa, MCF-7, and MDA-MB-231 cells at 4 and 24 h post-irradiation. Taken together, the morphological results support that the carbon ions induced autophagy in the tumor cells effectively.
Affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China.