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: To assess whether autophagy contributes to the resistance or sensitivity of tumor cells to high-LET radiation, HeLa cells were used in our experiment. Two key autophagy regulators, Beclin 1 and Atg5, were depleted with siRNA. Beclin 1 and Atg5 are required at vesicle nucleation and elongation steps, respectively.(27) These two genes were knocked down separately and together. The double KD result is shown in Figure 3(a). The degree of KD achieved for both genes was >50% at 24 and 48 h. Twenty-four hours after transfection, HeLa cells were irradiated with the carbon ions of 75 keV/μm. The inhibitory effect of siRNA on the proportion of AVO-positive cells was analyzed with flow cytometry. As shown in Figure 4(b), the KD of Beclin 1 together with Atg5 depressed the high-LET radiation-induced AVO formation significantly, whereas Beclin 1 or Atg5 KD alone had only a marginal effect. Shown in Figure 4(c) are the survival curves for HeLa cells under the conditions of irradiation, irradiation + siRNA Beclin 1, irradiation + siRNA Atg5, and irradiation + siRNA Beclin 1 and Atg5. The survival fractions of the cells treated with siRNA of both genes were significantly lower than those of the other three groups (P < 0.05 at the various doses).
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.