Introduction/Background Lysyl oxidase (LOX) is an enzyme engaged in the cross-linking of the extracellular matrix proteins. LOX proenzyme is secreted to extracellular space, then proteolitically cleaved resulting in the LOX enzyme and LOX propeptide (LOX-PP). Various studies showed contradictory results, indicating that LOX may act either as an oncogene or a tumor suppressor. More detailed analyses suggest that LOX enzyme may be responsible for oncogenic effects, while LOX-PP may act as tumor suppressor. Our aim was to investigate LOX-PP role in ovarian cancer cells.
Methodology Ovarian cancer cell lines (SKOV3, A2780, ES2) with stable LOX-PP overexpression were established using lentiviral transfer system. Cell lines were validated by semi-quantitive RT-PCR and immunoblotting. Cells proliferation were assessed by MTS assay. In vitro cytotoxicity assay was performed with two major drugs used in ovarian cancer treatment: cisplatin (0,1–20µM range) and paclitaxel (1,56 nM - 30µM range).
Results RT-PCR showed that the LOX-PP-containing cells had higher LOX-PP expression compared to control cells with an empty vector. Immunodetection was successful both in cells lysates and in culture medium suggesting that the protein is efficiently secreted. Cell proliferation assay showed lower proliferation rate of A2780_LOX-PP as compared to controls. No differences in proliferation rate was observed among cell lines SKOV3 and ES2. In vitro cytotoxicity assay demonstrated that LOX-PP overexpressing SKOV3 and A2780 cells were more sensitive to both cisplatin and paclitaxel. The A2780_ LOX-PP cells showed a 8,5% and 16% higher sensitivity to paclitaxel and cisplatin, respectively, while SKOV3¬_ LOX-PP cells showed 15% and 24% higher sensitivity to those drugs.
Conclusion LOX-PP seems to exert an anti-cancer function in ovarian cancer, either by decreasing cells proliferation rate and/or by sensitizing of cells to chemotherapeutic agents.
Disclosures The authors have no conflicts of interest to declare.
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