Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer |
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Authors: | F Cui W Wang D Wu X He J Wu M Wang |
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Institution: | 1.Department of Oncology, Nanfang Hospital,Southern Medical University,Guangzhou,People’s Republic of China;2.Department of Thoracic Surgery,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou,People’s Republic of China;3.Pharmaceutical Department,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou,People’s Republic of China |
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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. |
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