ABSTRACT
@#【Objective】To explore the effects and the possible mechanism of KPT- 8602，a novel selective inhibitor of nuclear export protein （XPO1），on proliferation，cell cycle and apoptosis in human histiocytic lymphoma cell line U937 cells.【Methods】U937 cells were treated with different concentrations of KPT- 8602. Cell viability was assessed by CCK-8 assay. The cell cycle distribution and the apoptosis rate were analyzed by flow cytometry. The proteins expression of XPO1，p-AKT，AKT，Cleaved Caspase-3，p21 were determined by Western blot. Fluorescence microscope was used in observing the intracellular location of XPO1. 【Results】 KPT- 8602 inhibited the growth of U937 cells in a dose- dependent（P<0.001）and time- dependent manner（P<0.001），but normal PBMC were unaffected. 48 h after treatment with KPT-8602，a higher proportion of cells in G1 phase was observed（P<0.001）and the apoptosis rate increased（P=0.016）with drug concentration in U937 cells. XPO1 protein expression of U937 cells was significantly higher than normal PBMC（P=0.003）. 48 h after treatment with KPT- 8602，the protein expression of XPO1 decreased（P=0.011），p-AKT decreased（P=0.011），and Cleaved Caspase- 3 increased（P=0.009）. In addition，the protein expression of p21，the cargo protein of XPO1，increased in both the nuclei and the cytoplasm（P<0.05）after treatment with KPT- 8602. XPO1 decreased in both the nuclei and the cytoplasm under the fluorescence microscope after treatment with KPT- 8602.【Conclusion】KPT- 8602 can inhibit the proliferation of U937 cells，block the cell cycle at G1 phase，and induce cell apoptosis，which may partially be attributed to the down-regulation of XPO1 and inhibition of PI3K/AKT signaling.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Yikunning (YKN, Chinese Traditional Medicine) on the expressions of bcl-2 and bax in rat ovaries during perimenopausal period.</p><p><b>METHODS</b>Thirty female Wistar rats during perimenopausal period were selected by unforced aging. Then the rats were divided into 3 groups randomly: YKN group, Livial control group and Aged control group. Ten young female Wistar rats were selected as young control group. Intragastric administrations were conducted for 4 weeks once daily continuously. The expressions of Bcl-2 Bax mRNAs and proteins in rat ovaries were detected by RT-PCR and Western blot.</p><p><b>RESULTS</b>The levels of Bcl-2, Bax mRNAs and proteins in rat ovaries in YKN group were higher than those in Aged control group, which showed differences among them (P < 0.01). The Bcl-2/Bax mRNA rate and protein rate in rat ovaries in YKN group were higher than those in Aged control group, which showed differences among them (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>YKN could increase the expressions of Bcl-2, Bax mRNAs and proteins and up-regulate the Bcl-2/Bax mRNA rate, protein rate in rat ovaries during perimenopausal period, which might be one of the molecular mechanisms of YKN postponed the ovarian failure and cured perimenopausal syndrome.</p>
Subject(s)
Animals , Female , Rats , Drugs, Chinese Herbal , Pharmacology , Ovary , Metabolism , Perimenopause , Physiology , Proto-Oncogene Proteins c-bcl-2 , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Rats, Wistar , Up-Regulation , bcl-2-Associated X Protein , Genetics , MetabolismABSTRACT
<p><b>AIM</b>To investigate the effects of soy isoflavones (SI) on the expression of Bax mRNA and Ca(2+) -ATPase activity in ovaries of perimenopause rats.</p><p><b>METHODS</b>The animal model of perimenopause rats was established by unforced aging. 12 month-old presenilins female Wistar rats were administered by intragastric (ig) with low (500 mg/kg), middle (158 mg/kg) and high (500 mg/kg) does of SI for 8 weeks. The expression of Bax mRNA in ovaries were detected by RT-PCR. Ca(2+) -ATPase activity in ovaries and MDA content and SOD activity in serum were detected by chemi-chromatometry.</p><p><b>RESULTS</b>Intervention of SI could significantly decrease the expression of Bax mRNA in ovaries and MDA content in serum, increase Ca(2+) -ATPase activity in ovaries and SOD activity in serum of presenilins rats (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Soy isoflavones could down-regulate the expression of Bax mRNA and increase Ca(2+) -ATPase activity in aged ovaries. It is probably one of the mechanisms to improve the function of aged ovaries in perimenopause rats.</p>