title: Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer.
abstract: Lung cancer, the most common malignancy, is still the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80 % of all lung cancers. Recent studies showed Cathepsin L (CTSL) is overexpressed in various cancerous tissues; however, the association between CTSL expression and EGFR-TKI resistance remains unknown. In this study, we investigated the expression of CTSL in lung cancer specimens and matched normal tissues by quantitative real-time PCR and IHC. The functional role of CTSL in resistant PC-9/GR cell line was investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that the level of CTSL expression was higher in NSCLC tissues compared with matched normal adjacent tissue samples, and CTSL was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking-down of CTSL in PC-9/GR cells could decrease cell proliferation and potentiate apoptosis induced by gefitinib, suggesting CTSL may contribute to gefitinib resistance in NSCLC. CTSL might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: F
authors.initials: F
authors.lastname: Cui
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, 510120, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, 510120, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, 510120, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.affiliation: Pharmaceutical Department, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, 510120, People's Republic of China. drwujy67@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, 510120, People's Republic of China. drwangxh@163.com.
authors.forename: M
authors.initials: M
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D056668:Cathepsin L / Q000032:analysis / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D011799:Quinazolines / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; C534281:CTSL protein, human; D056668:Cathepsin L; D000077156:Gefitinib
keywords: Apoptosis; CTSL; Chemoresistance; EGFR-TKI; Lung cancer; NSCLC; PC-9/GR cells; Proliferation