American Association for Cancer Research
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00085472can123516-sup-supp_fig_s2.pdf (414.63 kB)

Supplementary Figure S2 from Radioresistant Cancer Cells Can Be Conditioned to Enter Senescence by mTOR Inhibition

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posted on 2023-03-30, 21:28 authored by Hae Yun Nam, Myung Woul Han, Hyo Won Chang, Yoon Sun Lee, Myungjin Lee, Hyang Ju Lee, Byoung Wook Lee, Hee Jin Lee, Kyung Eun Lee, Min Kyo Jung, Hyesung Jeon, Seung-Ho Choi, Neung Hwa Park, Sang Yoon Kim, Seong Who Kim

Supplementary Figure S2 PDF - PDF file 414K, Activation of autophagy in AMC-HN-9 cells

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ARTICLE ABSTRACT

Autophagy is frequently activated in radioresistant cancer cells where it provides a cell survival strategy. The mTOR inhibitor rapamycin activates autophagy but paradoxically it also enhances radiosensitivity. In this study, we investigated the mechanisms of these opposing actions in radiation-resistant glioma or parotid carcinoma cells. Radiation treatment transiently enhanced autophagic flux for a period of 72 hours in these cells and treatment with rapamycin or the mTOR inhibitor PP242 potentiated this effect. However, these treatments also increased heterochromatin formation, irreversible growth arrest, and premature senescence, as defined by expression of senescence-associated β-galactosidase activity. This augmentation in radiosensitivity seemed to result from a restoration in the activity of the tumor suppressor RB and a suppression of RB-mediated E2F target genes. In tumor xenografts, we showed that administering rapamycin delayed tumor regrowth after irradiation and increased senescence-associated β-galactosidase staining in the tumor. Our findings suggest that a potent and persistent activation of autophagy by mTOR inhibitors, even in cancer cells where autophagy is occurring, can trigger premature senescence as a method to restore radiosensitivity. Cancer Res; 73(14); 4267–77. ©2013 AACR.