[Abstract unavailable

No abstract

Glioblastoma (GB) has a poor prognosis, despite current multimodality treatment. Beside surgical resection, adjuvant ionizing radiation (IR) combined with Temozolomide (TMZ) drug administration is the standard therapy for GB. This currently combined radio-chemotherapy treatment resulted in glial tumor cell death induction, whose main molecular death pathways are still not completely deciphered. In this study, the autophagy process was investigated, and in vitro modulated, in two different GB cell lines, T98G and U373MG (known to differ in their radiosensitivity), after IR or combined IR/TMZ treatments. T98G cells showed a high radiosensitivity (especially at low and intermediate doses), associated with autophagy activation, assessed by Beclin-1 and Atg-5 expression increase, LC3-I to LC3-II conversion and LC3B-GFP accumulation in autophagosomes of irradiated cells; differently, U373MG cells resulted less radiosensitive. Autophagy inhibition, using siRNA against BECN1 or ATG-7 genes, totally prevented decrease in viability after both IR and IR/TMZ treatments in the radiosensitive T98G cells, confirming the autophagy involvement in the cytotoxicity of these cells after the current GB treatment, contrary to U373MG cells. However, rapamycin-mediated autophagy, that further radiosensitized T98G, was able to promote radiosensitivty also in U373MG cells, suggesting a role of autophagy process in enhancing radiosensitivity. Taken together, these results might enforce the concept that autophagy-associated cell death might constitute a possible adjuvant therapeutic strategy to enhance the conventional GB treatment.

Autophagy is a so-called "self-eating" system responsible for degrading long-lived proteins and cytoplasmic organelles, whose products are recycled to maintain cellular homeostasis. This ability makes autophagy a good candidate for a survival mechanism in response to several stresses, including the tumor cell transformation. In particular, recent studies suggested that autophagy functions as a pro-death mechanism within different tumor contexts. It is, however, widely reported that autophagy represents both a survival mechanism or contributes directly to cell death fate. This interplay of the autophagy functions has been observed in many types of cancers and, in some cases, autophagy has been demonstrated to both promote and inhibit antitumor drug resistance. From a therapeutical point of view, the effects of the modulation of the tumor cell autophagic status, in response to ionizing radiations, are presently of particular relevance in oncology. Accordingly, this review also provides a perspective view on future works for exploring the modulation of autophagic indices in tumor cells as a novel molecular-based adjuvant strategy, in order to improve radiotherapy and chemotherapy effects in cancer patients.