title: Autophagy inhibition promotes paclitaxel-induced apoptosis in cancer cells.
abstract: Paclitaxel has been demonstrated to be an effective mitotic inhibitor and apoptosis inducer to treat aggressive malignancies. In this paper, we have provided a line of evidence that promotion of apoptotic cell death by paclitaxel was accompanied with induction of autophagy in A549 cells. Paclitaxel treatment could lead to the formation of acidic vesicular organelles (AVOs), the induction of Atg5, Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3) expressions, and the increase of punctate fluorescent signals in A549 cells pre-transfected with green fluorescent protein (GFP)-tagged LC3. Interestingly, paclitaxel-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or small interfering RNA against the autophagic gene beclin1. These findings suggest that paclitaxel-elicited autophagic response plays a protective role that impedes the eventual cell death, and inhibition of autophagy could be an adjunctive strategy for enhancing chemotherapeutic effect of paclitaxel as an antitumor agent.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
authors.forename: Guangmin
authors.initials: G
authors.lastname: Xi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Hu
authors.forename: Baolin
authors.initials: B
authors.lastname: Wu
authors.forename: Hanming
authors.initials: H
authors.lastname: Jiang
authors.forename: Charles Y F
authors.initials: CY
authors.lastname: Young
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Pang
authors.forename: Huiqing
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D017239:Paclitaxel