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. 2018 Feb 12;9(2):213. doi: 10.1038/s41419-017-0242-x

Fig. 4. Autophagy inhibition alleviates chemoresistance of glioblastoma cells.

Fig. 4

a Bafilomycin A1 (BAF) inhibited autophagy (lower panels) determined by the AAV-mRFP-GFP-LC3B reporter (*P < 0.05, **P < 0.01). Under normal (upper panels) and glucose starvation condition, there were significantly less yellow puncta with bafilomycin A1 than that without the treatment (*P < 0.05, **P < 0.01). b BAF downregulated the expression of ATG7 only slightly with normal (upper panels) but significantly with glucose starvation condition (lower panels) as examined by immunofluorescence staining. In addition, as shown in Fig. 3c, bafilomycin A1 repressed the expression/cleavage of ATG7 and LC3B under both normal and glucose starvation conditions determined by western blot analysis. NC normal glucose condition, GS glucose starvation condition. c Ki67 staining showed that GBM cell proliferation was significantly enhanced by bafilomycin A1 under glucose starvation conditions (**P < 0.01). After 2-day treatment of BAF, the percentage of Ki67-positive cells nearly doubled (26–50%) under glucose starvation condition (*P < 0.05, **P < 0.01). d BAF further sensitized glucose-starved GBM cells to chemotherapeutic drugs. The BAF enhanced the cytotoxicity under both normal and glucose starvation conditions. In particular, it effectively killed the subsets of cells that otherwise would have had entered quiescence, escaping from the chemotherapeutic drugs under the glucose starvation condition. As well, autophagy inhibition rendered the cells die faster and earlier (also refer to Supplementary Figure 3). e The synergistic effect of autophagy inhibition with chemotherapeutic drugs was independently confirmed by two other autophagy inhibitors of 3-MA and CQ. Nonetheless, the autophagy inhibitor MHY1485 failed to produce synergistic effect. 3-MA, 3-methyladenine, CQ hydroxychloroquine sulfate. f As revealed by the AAV-mRFP-GFP-LC3B reporter, both 3-MA and CQ effectively inhibited autophagy but MHY1485 failed to significantly repress autophagy, explaining its failure to produce synergistic effect