抑制Cathepsin L增加人肺癌A549细胞对紫杉醇的敏感性

Objective: To explore the A549 cells sensitivity to the PTX and the relationship between the Cathepsin L express quantity and its underlying mechanisms. In this study, we investigated a novel functional aspect of Cathepsin L in regulating resistance to paclitaxel (PTX), a commonly used chemotherapeutic drug in the treatment of lung cancer. Method: We established Cathepsin L knockdown A549 lines by transfecting cells with Cathepsin L shRNA plasmids or treating wiInhibition of Cathepsin L increased sensitivity to paclitaxel in human lung cancer A549 cellsth appropriate dose of Cathepsin L inhibitor (Z-FY-CHO). The viability of cells was measured by MTT assay, and cell proliferation was detected by colony formation assay. Western blot and immunofluorescence served to study treatment effects on Cathepsin L and several signaling associated with drug resistance. Result: We found that the protein level of Cathepsin L was increased in A549 cells treated with PTX, implying a possibility that Cathepsin L may be involved in regulating sensitivity of A549 cell to PTX. Furthermore, MTT assay and colony formation assay show that silencing of Cathepsin L attenuates cell viability and proliferation ability of the A549 cells, indicating that suppression of Cathepsin L indeed enhanced the sensitivity of tumor cells to PTX. In addition, we investigated EGFR, ERK and PI3K-Akt signaling pathway, which are associated with drug resistance, the result suggest that Cathepsin L may regulated chemotherapy resistance by prohibiting AKT and ERK phosphorylation. Conclusion：Our results revealed a new mechanism to determine the Cathepsin L involvement in regulating drug resistance and the Cathepsin L may be exploited as a new target for enhancing the efficacy of chemotherapeutics.