peoniflorin and Multiple-Myeloma

Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism.. ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial function by measuring cell viability and mitochondrial quality and labeling mitochondria with MitoTracker Green. Nerve injury in mice with BiPN was assessed by behavioral tests, evaluation of motor nerve conduction velocity, hematoxylin-eosin (HE) staining, electron microscopy and analysis of the levels of reactive oxygen species (ROS). Western blotting and immunohistochemistry (IHC) were used to assess the expression of autophagy-related proteins.. In MM patients, IL6 levels were positively correlated with the degree of PN. The results of bioinformatics analysis suggested that paeoniflorin ameliorated PN by altering inflammation levels and mitochondrial autophagy. Paeoniflorin increased PC12 cell viability and mitochondrial autophagy levels, alleviated mitochondrial damage, and reduced IL6 levels. In addition, paeoniflorin effectively improved the behavior of mice with BiPN, relieved sciatic nerve injury in mice, increased the expression of LC3II/I, beclin-1, and Parkin in sciatic nerve cells, and increased the expression of LC3B and Parkin in the nerve tissue.. The present study confirmed that paeoniflorin significantly ameliorated peripheral neuropathy (PN) caused by bortezomib, possibly by reducing IL6 levels to regulate PARKIN-mediated mitochondrial autophagy and mitochondrial damage.

Topics: Animals; Autophagy; Bortezomib; Glucosides; Interleukin-6; Mice; Mitochondria; Monoterpenes; Multiple Myeloma; Peripheral Nervous System Diseases; Quality of Life; Ubiquitin-Protein Ligases

Multiple myeloma (MM) is a type of cancer characterized by the excessive proliferation of malignant plasma cells. In China, the incidence of MM has been increasing annually. Paeoniflorin exerts numerous functions, including coronary vessel expansion, and anti‑inflammation and anticancer activities. The present study aimed to investigate the effects of paeoniflorin on the proliferation and apoptosis of SKO‑007 MM cells, via its effects on the regulation of matrix metalloproteinase‑2 (MMP‑2) and microRNA (miR)‑29b. In the present study, an MTT assay was used to analyze the proliferation of SKO‑007 cells treated with paeoniflorin. Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis and caspase‑3 activation assays were used to detect the levels of cellular apoptosis. The expression levels of MMP‑2 and miR‑29b were detected using gelatin zymography and quantitative‑polymerase chain reaction, respectively. In addition, miR‑29b and anti‑miR‑29b plasmids were transfected into SKO‑007 cells, and the effects of paeoniflorin on cell proliferation and apoptosis were subsequently detected. The results of the present in vitro studies demonstrated that paeoniflorin was able to inhibit the proliferation of SKO‑007 cells in a dose‑ and time‑dependent manner. Furthermore, paeoniflorin effectively increased cell apoptosis, and augmented the activation of caspase‑3 and caspase‑9 in the SKO‑007 cells. The expression levels of MMP‑2 were suppressed following treatment of the SKO‑007 cells with paeoniflorin. In addition, paeoniflorin was able to induce the expression of miR‑29b. Notably, the results of the present study indicated that miR‑29b expression may control the expression of MMP‑2 in SKO‑007 cells. In conclusion, the present study demonstrated that paeoniflorin was able to inhibit cell proliferation and promote apoptosis of MM cells by suppressing the expression of MMP‑2, via the upregulation of miR‑29b.

Topics: Apoptosis; Biomarkers; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Glucosides; Humans; Matrix Metalloproteinase 2; MicroRNAs; Monoterpenes; Multiple Myeloma