Study of Ciclopirox Olamine Inhibiting Human Glioma Cell SHG44 Growth and the Underlying Mechanism
Han Shengnan1,2, Gong Shiwei1,2, Fei Mingming1,2, Shangguan Fugen1,2, Lü Bin1,2*
The aim of this study was to investigate the effects and molecular mechanism of ciclopirox olamine (CPX) inhibiting the growth of human glioma cell SHG44. In this study, human glioma cell line SHG44 was treated with a gradient concentration of CPX, then the half maximal inhibitory concentration (IC50) and cell proliferation ability of the CPX treated SHG44 cells were determined by MTT assay. In addition, the clone-forming ability was detected to confirm the effect of CPX on SHG44 cell growth. Moreover, the transwell cell migration and invasion assays were performed to study the effects of CPX on the capacity of cell motility and invasiveness. Intracellular reactive oxygen species (ROS), mitochondrial ROS, and apoptosis were detected by flow cytometry. Seahorse XF96 Flux analyzer was used to measure the oxygen consumption rate (OCR), and Real-time PCR (qPCR) as well as Western blot were applied to detect the mRNA and protein levels. Our results showed that SHG44 cells were sensitive to CPX treatment. CPX could reduce both the mRNA and protein expression levels of STAT3, and thus inhibiting the migration and invasion of SHG44 cells. Moreover, CPX treatment significantly enhances the accumulation of mitochondrial ROS, which leads to the impairement of mitochondrial function, and thus inhibiting cell growth and promoting apoptosis. Collectively, our findings demonstrated that CPX could inhibit the growth of SHG44 cells, which may be developed as a drug for the treatment of glioma.
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