Autophagic flux response and glioblastoma sensitivity to radiation
<b>Objective: </b> Glioblastoma is the most common primary brain tumor in adults and one of the most lethal human tumors. It constitutes a unique non-metastasizing human tumor model with high resistance to radiotherapy and chemotherapy. The current study investigates the association betw...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2018-09-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1181 |
| _version_ | 1818107497705111552 |
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| author | Achilleas G. Mitrakas Dimitra Kalamida Alexandra Giatromanolaki Stamatia Pouliliou Avgi Tsolou Rafail Kyranas Michael I. Koukourakis |
| author_facet | Achilleas G. Mitrakas Dimitra Kalamida Alexandra Giatromanolaki Stamatia Pouliliou Avgi Tsolou Rafail Kyranas Michael I. Koukourakis |
| author_sort | Achilleas G. Mitrakas |
| collection | DOAJ |
| description | <b>Objective: </b> Glioblastoma is the most common primary brain tumor in adults and one of the most lethal human tumors. It constitutes a unique non-metastasizing human tumor model with high resistance to radiotherapy and chemotherapy. The current study investigates the association between autophagic flux and glioblastoma cell resistance. <b>Methods: </b> The expression kinetics of autophagy- and lysosome-related proteins following exposure of two glioblastoma cell lines (T98 and U87) to clinically relevant radiation doses was examined. Then, the response of cells resistant to radiotherapy and chemotherapy was investigated after silencing of <i>LC3A</i>, <i>LC3B</i>, and <i>TFEB</i> genes <i>in vitro</i> and <i>in vivo</i>. <b>Results: </b> Following irradiation with 4 Gy, the relatively radioresistant T98 cells exhibited enhanced autophagic flux. The more radiosensitive U87 cell line suffered a blockage of autophagic flux. Silencing of <i>LC3A</i>, <i>LC3B</i>, and <i>TFEB</i> genes <i>in vitro</i>, significantly sensitized cells to radiotherapy and temozolomide (U87: <i>P</i> < 0.01 and < 0.05, respectively; T98: <i>P</i> < 0.01 and < 0.01, respectively). Silencing of the LC3A gene sensitized mouse xenografts to radiation. <b>Conclusions: </b> Autophagy in cancer cells may be a key factor of radio-resistance and chemo-resistance in glioblastoma cells. Blocking autophagy may improve the efficacy of radiochemotherapy for glioblastoma patients. |
| first_indexed | 2024-12-11T02:00:25Z |
| format | Article |
| id | doaj.art-285dadff2c9548bca4472b9a967674d7 |
| institution | Directory Open Access Journal |
| issn | 2095-3941 2095-3941 |
| language | English |
| last_indexed | 2024-12-11T02:00:25Z |
| publishDate | 2018-09-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-285dadff2c9548bca4472b9a967674d72022-12-22T01:24:30ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412095-39412018-09-0115326027410.20892/j.issn.2095-3941.2017.01732017000173Autophagic flux response and glioblastoma sensitivity to radiationAchilleas G. Mitrakas0Dimitra Kalamida1Alexandra Giatromanolaki2Stamatia Pouliliou3Avgi Tsolou4Rafail Kyranas5Michael I. Koukourakis6Department of Radiotherapy/Oncology;Department of Radiotherapy/Oncology;Department of Pathology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, GreeceDepartment of Radiotherapy/Oncology;Department of Radiotherapy/Oncology;Department of Radiotherapy/Oncology;Department of Radiotherapy/Oncology;<b>Objective: </b> Glioblastoma is the most common primary brain tumor in adults and one of the most lethal human tumors. It constitutes a unique non-metastasizing human tumor model with high resistance to radiotherapy and chemotherapy. The current study investigates the association between autophagic flux and glioblastoma cell resistance. <b>Methods: </b> The expression kinetics of autophagy- and lysosome-related proteins following exposure of two glioblastoma cell lines (T98 and U87) to clinically relevant radiation doses was examined. Then, the response of cells resistant to radiotherapy and chemotherapy was investigated after silencing of <i>LC3A</i>, <i>LC3B</i>, and <i>TFEB</i> genes <i>in vitro</i> and <i>in vivo</i>. <b>Results: </b> Following irradiation with 4 Gy, the relatively radioresistant T98 cells exhibited enhanced autophagic flux. The more radiosensitive U87 cell line suffered a blockage of autophagic flux. Silencing of <i>LC3A</i>, <i>LC3B</i>, and <i>TFEB</i> genes <i>in vitro</i>, significantly sensitized cells to radiotherapy and temozolomide (U87: <i>P</i> < 0.01 and < 0.05, respectively; T98: <i>P</i> < 0.01 and < 0.01, respectively). Silencing of the LC3A gene sensitized mouse xenografts to radiation. <b>Conclusions: </b> Autophagy in cancer cells may be a key factor of radio-resistance and chemo-resistance in glioblastoma cells. Blocking autophagy may improve the efficacy of radiochemotherapy for glioblastoma patients.http://www.cancerbiomed.org/index.php/cocr/article/view/1181GlioblastomaautophagyradiationtemozolomideTFEB |
| spellingShingle | Achilleas G. Mitrakas Dimitra Kalamida Alexandra Giatromanolaki Stamatia Pouliliou Avgi Tsolou Rafail Kyranas Michael I. Koukourakis Autophagic flux response and glioblastoma sensitivity to radiation Cancer Biology & Medicine Glioblastoma autophagy radiation temozolomide TFEB |
| title | Autophagic flux response and glioblastoma sensitivity to radiation |
| title_full | Autophagic flux response and glioblastoma sensitivity to radiation |
| title_fullStr | Autophagic flux response and glioblastoma sensitivity to radiation |
| title_full_unstemmed | Autophagic flux response and glioblastoma sensitivity to radiation |
| title_short | Autophagic flux response and glioblastoma sensitivity to radiation |
| title_sort | autophagic flux response and glioblastoma sensitivity to radiation |
| topic | Glioblastoma autophagy radiation temozolomide TFEB |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1181 |
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