Identification of differentially expressed genes in MG63 osteosarcoma cells with drug‑resistance by microarray analysis.

Osteosarcoma is the most common type of primary malignant bone tumor, with extremely poor prognosis in patients with metastatic disease and resistance to therapy, such as multidrug regimens. The mechanisms of drug resistance are quite complex and have not been fully elucidated; thus, novel therapeutic targets should be identified to alleviate drug resistance in osteosarcoma. In the present study, the transcriptomes of the human osteosarcoma cell line MG63 and vincristine (VCR)‑resistant MG63 cells were compared by microarray analysis.

LIM kinase 1 serves an important role in the multidrug resistance of osteosarcoma cells.

Multidrug resistance (MDR) is a major challenge for the management of the majority of cancers. The precise molecular mechanisms of MDR remain elusive. In a previous study, a multidrug resistant osteosarcoma model [MG63/vincristine (VCR)] was established by intermittent exposure of MG63 cells to gradually increasing concentrations of VCR.

Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance.

Multidrug resistance (MDR) is a challenge for the treatment of cancer and the underlying molecular mechanisms remain elusive. The current study exposed MG63 osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish four VCR‑resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug resistance indices (RI) of these sublines was detected with the CCK‑8 assay and determined to be163, 476, 1,247, and 2,707‑fold higher than that of parental cells, respectively.

SO(2)-induced neurotoxicity is mediated by cyclooxygenases-2-derived prostaglandin E(2) and its downstream signaling pathway in rat hippocampal neurons.

Sulfur dioxide (SO(2)) pollution in atmospheric environment is involved in neurotoxicity and increased risk for hospitalization and mortality of many brain disorders; however, our understanding of the mechanisms by which SO(2) caused harmful insults on neurons remains elusive. Here, we show that SO(2) exposure produced a neuronal insult, and the neurotoxic effect was likely via stimulating cyclooxygenase-2 (COX-2) elevation by activation of nuclear factor-κB (NF-κB) activity and its acting on the promoter-distal NF-κB-binding site of COX-2 promoter. The action of SO(2) on elevating COX-2 ultimately appeared to be dependent on the increased production of arachidonic acid-derived prostaglandins, mainly prostaglandin E(2) (PGE(2)), and functioning of its EP2/4 receptors.