title: Inhibition of autophagy by autophagic inhibitors enhances apoptosis induced by bortezomib in non-small cell lung cancer cells.
abstract: Bortezomib is a novel proteasome inhibitor that has promising antitumor activity against various cancer cells. We have assessed its antitumor activity in non-small cell lung cancer (NSCLC) A549 and H157 cells in vitro where it inhibited cell growth and induced apoptosis, which was associated with cytochrome c release and caspase-3 activation. Bortezomib upregulated autophagic-related proteins, the Atg12-Atg5 complex and LC3-II, which indicated autophagy had occurred. The combination of bortezomib with autophagic inhibitor 3-methyladenine or chloroquine significantly enhanced suppression of cell growth and apoptosis induced by bortezomib in A549 and H157 cells. Our study indicated that inhibition of both proteasome and autophagy has great potential for NSCLC treatment.
authors.affiliation: Department of Cardiovascular, Regenerative Medicine and Tissue Engineering, First Affiliated Hospital of Jilin University, Changchun, 130021, Jilin, China, sunmingli130@163.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: Wu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ji
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Mingli
authors.initials: M
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects*; D001897:Boronic Acids / Q000378:metabolism*; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung; D053148:Caspase 3 / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000032:analysis; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D011719:Pyrazines / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D045304:Cytochromes c; D053148:Caspase 3