title: An autophagy inhibitor enhances the inhibition of cell proliferation             induced by a proteasome inhibitor in MCF-7 cells.
abstract: The ubiquitin-proteasome system and the autophagy-lysosome pathway are the             two main routes for eukaryotic intracellular protein clearance. Inhibition of             proteasome activity leads to cell death. Due to the dual roles of autophagy in             tumor cell survival and death, the effect of suppression of autophagy on breast             cancer cells remains to be elucidated. We investigated whether inhibition of the             proteasome is capable of inducing autophagy, and we assessed the effect of combined             inhibition of the proteasome and autophagy on human breast cancer MCF-7 cells.             The proteasome inhibitor bortezomib was used to induce autophagy in MCF-7 cells,             and the effect of autophagy on the proliferation of MCF-7 cells was investigated             using the autophagy inhibitor 3-MA. Cell viability was measured by MTT assay.             The expression of autophagy‑related proteins was determined by Western blot analysis             and the GFP-LC3 redistribution was detected using a fluorescence microscope after             MCF-7 cells were infected with a GFP-LC3-expressing adenovirus. MCF-7 cell proliferation             was inhibited and autophagy was activated in the same dose‑dependent manner. Bortezomib             induced a dose‑dependent increase in LC3-II. However, when MCF-7 cells were co-treated             with bortezomib and 3-MA, 3-MA blocked the increase in LC3-II protein expression             and led to a significant inhibition of cell proliferation. Inhibition of the proteasome             may induce autophagy in human breast cancer MCF-7 cells and 3-MA could inhibit             autophagy induced by the proteasome inhibitor. A combination of 3-MA and bortezomib             increases cell death. These findings indicate that suppression of the two intracellular             degradation systems may shed new light on breast cancer control.
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Guannan
authors.initials: G
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Wei
authors.forename: Yi
authors.initials: Y
authors.lastname: Tu
authors.forename: Hexiang
authors.initials: H
authors.lastname: Tong
authors.forename: Shengrong
authors.initials: S
authors.lastname: Sun
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D061988:Proteasome Inhibitors; D011719:Pyrazines; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; D000225:Adenine