Significance of PLSCR1 in Matrine Induced Differentiation of ATRA Resistant APL Cells / 中国中西医结合杂志
Chinese Journal of Integrated Traditional and Western Medicine
; (12): 1345-1350, 2015.
Article
在 Zh
| WPRIM
| ID: wpr-286384
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway.</p><p><b>METHODS</b>NB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes.</p><p><b>RESULTS</b>MAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>MAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.</p>
全文:
1
索引:
WPRIM
主要主题:
Quinolizines
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Tretinoin
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RNA, Messenger
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Tumor Cells, Cultured
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Leukemia, Promyelocytic, Acute
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Signal Transduction
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Down-Regulation
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Cell Differentiation
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Up-Regulation
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Cell Line, Tumor
限制:
Humans
语言:
Zh
期刊:
Chinese Journal of Integrated Traditional and Western Medicine
年:
2015
类型:
Article