Cao Haiwu, Zhao Xiaohong, Lu Shiyun, Wang Zhi
Department of Hematology, Wuxi Second People's Hospital, Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.
Exp Ther Med. 2018 Jun;15(6):5431-5435. doi: 10.3892/etm.2018.6111. Epub 2018 Apr 30.
The aim of the current study was to measure the expression of acetyl-N-Ser-Asp-Lys-Pro (ACSDKP) in patients with acute myeloid leukemia (AML) and the effect of prolyl oligopeptidase inhibitor (POPi) on the bone marrow stromal cells of these patients. Serum and bone marrow stromal cell samples were collected from 33 patients with AML admitted to Wuxi Second People's Hospital, Nanjing Medical University between September 2011 and August 2016. ACSDKP levels were measured using a highly specific competitive enzyme immunoassay (EIA). Bone marrow stromal cells were treated with synthetic ACSDKP (10 µM/ml) or different concentrations of POPi S17092 (25, 50 and 100 µg/ml). Cells that received no treatment were used as control. An MTT assay was conducted to measure the proliferation of bone marrow stromal cells. The results demonstrated that serum levels of ACSDKP in patients with AML were significantly higher than those of controls (P<0.05). Following treatment with ACSDKP, cell proliferation was significantly increased compared with untreated cells (P<0.05). However, following treatment with different concentrations of POPi, the expression of ACSDKP was significantly decreased in a dose-dependent manner (P<0.05). Furthermore, the proliferation of bone marrow stromal cells was also decreased in a dose-dependent manner. Therefore, the present study demonstrated that ACSDKP levels were increased in the serum and bone marrow stromal cells of patients with AML and that ACSDKP promoted the proliferation of bone marrow stromal cells of these patients, which was inhibited by POPi. These results may identify a novel target for the treatment of AML.
本研究的目的是检测急性髓系白血病(AML)患者中乙酰化N - 丝氨酸 - 天冬氨酸 - 赖氨酸 - 脯氨酸(ACSDKP)的表达情况,以及脯氨酰寡肽酶抑制剂(POPi)对这些患者骨髓基质细胞的影响。2011年9月至2016年8月期间,从南京医科大学附属无锡第二人民医院收治的33例AML患者中采集血清和骨髓基质细胞样本。采用高特异性竞争酶免疫测定法(EIA)检测ACSDKP水平。用合成的ACSDKP(10 µM/ml)或不同浓度的POPi S17092(25、50和100 µg/ml)处理骨髓基质细胞。未接受处理的细胞用作对照。进行MTT试验以检测骨髓基质细胞的增殖情况。结果表明,AML患者血清中ACSDKP水平显著高于对照组(P<0.05)。用ACSDKP处理后,与未处理细胞相比,细胞增殖显著增加(P<0.05)。然而,用不同浓度的POPi处理后,ACSDKP的表达呈剂量依赖性显著降低(P<0.05)。此外,骨髓基质细胞的增殖也呈剂量依赖性降低。因此,本研究表明,AML患者血清和骨髓基质细胞中ACSDKP水平升高,且ACSDKP促进这些患者骨髓基质细胞的增殖,而POPi可抑制该增殖。这些结果可能为AML的治疗确定一个新靶点。