TIMP3 regulates osteosarcoma cell migration, invasion, and chemotherapeutic resistances

摘要: Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix (MMPs) to limit degradation the extracellular matrix. Low levels TIMP3 have been demonstrated in cancer tissues at advanced clinical stages, with positive distant metastasis and chemotherapeutic resistance. We examined role osteosarcoma (OS) cell invasiveness chemoresistance. was overexpressed or knocked down human OS lines Saos2 MG63. Cell migration invasion capacities were then evaluated using Transwell assays, resistance cisplatin assessed by CCK-8 assay flow cytometry. Real-time PCR western blotting used investigate activation signaling pathways downstream TIMP3. Overexpression inhibited MG63 cells, while knockdown had opposite effect. survival after exposure overexpression both cells. Consistently, downregulation gene expression significantly decreased sensitivity cells treatment. MMP1, MMP2, Bcl-2, Akt1 all downregulated following overexpression, Bax cleaved caspase-3 upregulated. effects on regulation these genes. Taken together, our findings suggest as a new target for inhibition progression