title: [Effect of midazolam on mantle cell lymphoma JeKo-1 cell line and its relevant mechanisms].
abstract: This study was aimed to explore the effect of midazolam on mantle cell lymphoma cell line JeKo-1 and the relevant mechanisms. Effects of midazolam on the proliferation and apoptosis of JeKo-1 cells were observed by CCK8 assay and flow cytometry, respectively. Effect of midazolam on the expression of BCL-2, cytochrome C (Cyto-C), pro-caspase-9, pro-caspase-8 and pro-caspase-3 protein were detected by Western blot. The results showed that midazolam could inhibit the growth of JeKo-1 cells significantly and the concentration of 50% growth inhibition (IC50) at 48 hours was approximately 40 µmol/L. After treatment with 20, 40, 80 µmol/L midazolam for 48 hours, a dose-dependent apoptosis of JeKo-1 cells could be observed. Meanwhile, a dose-dependent reduction of BCL-2, pro-caspase-9 and pro-caspase-3 protein expression and increase of Cyto-C protein expression in JeKo-1 cells were found, but the expression of pro-caspase-8 protein did not change. It is concluded that midazolam possibly initiates the mitochondrial pathway, not the death receptor pathway, by reducing the expression of BCL-2, leading in turn to the releasing of Cyto-C in mitochondria, then activating caspase-9 and caspase-3 protein, triggers the caspase cascade, and induces the apoptosis of JeKo-1 cells ultimately.
authors.affiliation: Department of Anesthesia, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Hong
authors.affiliation: Department of Anesthesia, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
authors.forename: Shan-Hu
authors.initials: SH
authors.lastname: Wu
authors.affiliation: Department of Anesthesia, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
authors.forename: Wei-Huang
authors.initials: WH
authors.lastname: Zhuang
authors.affiliation: Scientific Research Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China. E-mail: hongjinquan1114@163.com.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism*; D008874:Midazolam / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D008874:Midazolam