Objective:To explore the role and mechanisms ofω-3 polyunsaturated fatty acids (ω-3PUFAs) alone or in combination with dexamethasone (DEX) in inducing cell apoptosis and reversing drug resistance in multiple myeloma (MM). Methods:DEX-resistant MM cell line MM1R was treated with different concentrations of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) alone or in combination with DEX for 24 or 48 h. Cel proliferation was detected by MTT assay. Cel cycle and apoptosis were measured by flow cytometry. Expression levels of apoptosis-related proteins were analyzed by Western blot. Two-tailed, unpaired Student's t-test was used to compare the two treatment groups. A value of P<0.05 was considered statistically significant. Results:MM1R proliferation was inhibited by different concentrations (10, 20, 50, and 100μM) of EPA or DHA alone or in combination with 10μM DEX in a dose-and time-dependent manner. The inhibition effect was significantly higher in combinative groups than in single EPA or DHA treatment group (P=0.014, P=0.032). The percentage of G0/G1 phase and cell apoptosis rate in MM1R treated with different concentrations of EPA or DHA alone increased in a dose-dependent manner. This percentage was also significantly higher in the combinative groups than in the single EPA or DHA treatment group (P=0.015, P=0.004). The expression levels of cleaved caspase-3 and Bax were upregulated, whereas those of pro-caspase-3 and BCL-2 were downregulated in a dose-dependent manner. Drug resistance gradually decreased in MM1R cells at different concentrations of EPA or DHA with the increase of drug concentration. The reversal fold also increased gradual y, whereas the cel s decreased in the two drug-combination groups compared with the single-drug group. Moreover, the drug-resistance reversal index increased significantly. Conclusion:ω-3PUFAs can inhibit DEX-resistant MM cell proliferation, arrest cell cycle, and induce cell apoptosis.ω-3PUFAs also exhibit a synergistic anti-resistanteffect in combination with DEX. Furthermore,ω-3PUFAs can serve as novel effective drugs for MM treatment.

BACKGROUND: At present, the relationship between diabetic nephropathy and osteoprotagerin remains poorly understood. OBJECTIVE: To investigate the correlation between bone mineral density (BMD) and serum osteoprotagerin changes in patients with 2 type diabetic nephropathy. METHODS: Totally 104 patients with 2 type diabetes were divided following 5 groups according to glomerular filtration rate: simple diabetes, mild renal injury, moderate renal injury, severe renal injury, and renal failure groups. Additional 20 healthy people were selected as the control group. The level of serum osteoprotegerin was measured by ELISA. Meantime, levels of serum calcium, phosphonium, alkaline phosphatase, creatinine, urea nitrogen, and glycosylatad hemoglobin were measured by. the automatic biochemistry analyzer. The bone mineral density of entopic L_(2-4) was determined by dual X-ray bone density equipment. The whole data was analyzed by multiple regression correlation analysis. RESULTS AND CONCLUSION: The level of serum osteoprotegerin in patients with diabetic nephropathy was obviously greater than that of the healthy people (P < 0.05), but BMD of the mild renal injury, moderate renal injury, severe renal injury, and renal failure groups was obviously lower than that of the healthy people (P < 0.05). Generally, the worse renal function accompanied by higher osteoprotegerin level, and lower BMD. There was a negative correlation between ostaoprotegerin level and BMD in patients with diabetic nephropathy (r=-0.497, P < 0.01). However, the relationships between osteoprotegedn level and diabetic duration (r=0.566, P < 0.01), serum creatinine level (r=0.772, P < 0.01), serum urea nitrogen level (r=0.708, P < 0.01), serum phosphonium level (r=0.329, P < 0.01), or serum intact parathyroid hormone level (F=0.702, P < 0.01) were positive. Meantime, the serum phosphonium level had negative correlation to serum calcium level (r=-0.505, P < 0.01). it demonstrated that when the renal function got worse in diabetic nephropathy patients, the serum osteoprotegerin level was increasing accompanied by BMD decreasing. The osteoprotegerin level presents a negative correlation to BMD and serum calcium level, but positive to diabetic duration, serum creatinine, serum urea nitrogen, serum phosphonium and serum intact parathyroid hormone levels.

Chemical and Drug Induced Liver Injury ; Humans ; Thrombocytopenia