title: [Effects of arsenic trioxide or retinoic acid on mRNA and protein expression of tissue factor and thrombomodulin and procoagulant activity in NB4 cells].
abstract: To investigate the effect of arsenic trioxide (As(2)O(3)) or all-trans retinoic acid (ATRA) on the mRNA and protein expression of tissue factor (TF) and thrombomodulin (TM) and procoagulant activity (PCA) in NB4 cells. The NB4 cells were cultured in vitro and treated with As(2)O(3) or ATRA, expression of TF and TM antigen, and PCA change of treated NB4 cells were detected with ELISA, TF and TM mRNA transcription on the NB4 cells was assayed with reversed transcription polymerase chain reaction (RT-PCR). The results showed that 1 micromol/L As(2)O(3) and 1 micromol/L ATRA both gradually downregulated the expression of TF antigen and mRNA on NB4 cells, a human promyelocytic leukemia cell line, in time-dependent manner, as compared with control. The levels of TF antigen expression in AS(2)O(3) group were 13.3 +/- 1.8, 8.6 +/- 1.9, 10.8 +/- 1.5, 2.0 +/- 0.6 and 2.6 +/- 0.9 ng/10(7) respectively; while the levels of TF antigen expression in ATRA group were 12.4 +/- 1.1, 11.3 +/- 1.8, 5.7 +/- 1.7, 2.8 +/- 0.8 and 2.0 +/- 0.6 ng/10(7) at 24, 48, 72, 96 and 120 hours respectively (P<0.05). The procoagulant activity (PCA) of NB4 cells was decreased, blood coagulation times were 123.5 +/- 10.5, 156.3 +/- 11.6, 179.3 +/- 15.3, 248.9 +/- 20.1, 312.0 +/- 29.8 seconds in As(2)O(3) groups, respectively; 76.4 +/- 5.6, 146.8 +/- 10.9, 198.2 +/- 15.6, 265.8 +/- 20.6 and 363.8 +/- 31.9 seconds in ATRA groups respectively at 24, 48, 72, 96 and 120 hours (P<0.05). ATRA upregulated TM antigen expression on NB4 cells. It is concluded that the As(2)O(3) and ATRA decrease mRNA transcription of TF, downregulate expression of TF and reduce procoagulant activity in NB4 cells. The TM transcription and expression upregulated by ATRA may alleviate dysfunction of coagulation in APL.
authors.affiliation: Institute of Hematology and People Hospital, Peking University, Beijing 100044, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Xia
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Guan-Xin
authors.initials: GX
authors.lastname: Shen
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Wei
authors.forename: Shan-Jun
authors.initials: SJ
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018180:Thrombomodulin / Q000096:biosynthesis* / Q000235:genetics; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; D018180:Thrombomodulin; C053675:endothelial cell procoagulant activity; D014212:Tretinoin; D013925:Thromboplastin; D000077237:Arsenic Trioxide