title: Caveolin-1 regulates cell apoptosis and invasion ability in paclitaxel-induced multidrug-resistant A549 lung cancer cells.
abstract: The aim of the study was to investigate the effect and potential mechanism of caveolin-1 (Cav1) knockdown in paclitaxel-resistant lung cancer A549/Taxol cells. The human paclitaxel-resistant lung cancer cell line A549/Taxol was transfected with a Cav1 shRNA lentiviral vector. Interference efficiency for Cav1 was detected by real-time PCR and Western blotting. A MTT assay was used to determine cell proliferation, and flow cytometry was used to detect the cell cycle stage and apoptosis. Cell migration and invasion capability were detected by a transwell assay. Protein levels of related signaling molecules were detected by Western blotting. We successfully constructed a stable A549/Taxol cell line expressing low levels of Cav1. Cav1 knockdown significantly inhibited cell proliferation and induced G0/G1 arrest and cell apoptosis in vitro and in vivo. In addition, these effects correlated significantly with a reduction in cyclin D1 expression and activation of the Bcl-2/Bax-mediated mitochondrial apoptosis pathway. Furthermore, knockdown of Cav1 inhibited cell migration and invasion, and this may be related to the inhibition of AKT and the subsequent decreased protein expression of MMP2, MMP7 and MMP9.
authors.affiliation: Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai 200065, China ; Department of Pathology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University Shanghai 200030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai 200065, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Thoracic-Cardiovascular Surgery, Tongji Hospital of Tongji University 389 Xincun Rd, Shanghai, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai 200065, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051242:Caveolin 1; D017239:Paclitaxel
keywords: A549/Taxol; Caveolin-1; apoptosis; invasion; multidrug-resistant