评价化疗药物和硫代氨基脲复合物对急性淋巴细胞白血病SNHG16表达改变的影响

Fatemeh Erfanipour, Fatemeh Ghorbani, S. Mirzaahmadi, Golnaz Asaadi Tehrani
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摘要

背景:急性淋巴细胞白血病(Acute lymphoblastic leukemia, ALL)是一种儿童和成人皆可患的恶性疾病。它始于骨髓(骨内柔软的海绵状组织),未成熟的白细胞或淋巴细胞在那里形成。本研究旨在比较化疗药物甲氨蝶呤(MTX)、环磷酰胺、阿糖胞苷(阿拉- c)、巯基嘌呤(6mp)与硫代氨基脲(TSCZ)的镍(Ni)、铜(Cu)配合物对ALL细胞系小核RNA宿主基因16(SNHG16)长链非编码RNA (lncRNA)表达变化的影响。材料与方法:本实验研究采用MTX、CP、Ara-C、6mp、TSCZ的Ni、Cu配合物等不同浓度的化疗药物。将Jurkat E6.1细胞系按不同的组和时间(24、48、72h)传代,然后用化疗药物处理。提取RNA、合成cDNA后,采用Real-Time PCR检测SNHG16基因表达,Rest软件分析结果。结果:结果显示,24h内MTX复合物(0.77,0.72)、CP复合物(0.61,0.7)、ara-C复合物(0.78,0.87)、Cu复合物(0.91,0.95)、Ni复合物(0.94,0.79)以及复合物1(0.73)、2(0.94)显著降低SNHG16基因的表达(P<0.001)。48h内,在CP(0.86, 0.89)、Ara-C(0.94, 0.97)和Cu(0.96)、Ni(0.98)复合物的影响下,基因表达继续下降(P<0.001)。化疗药物以1μM ara-C和5μM 6mp联合用药效果最大(P<0.001)。结论:基因表达分析是鉴别ALL患者标准诱导化疗影响通路的一种可行方法。这一发现促进了新的靶向药物和生物标志物的发展,以分类疾病的侵袭性和评估治疗反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluating the effects of chemotherapy drugs and thiosemicarbazone complexes on the alteration of SNHG16 expression in Acute Lymphoblastic Leukemia
Background: Acute lymphoblastic leukemia (ALL) is a malignant disease that afflicts both children and adults. It starts from the bone marrow (soft and spongy tissue inside the bone) where immature white blood cells or lymphocytes are formed. This study aims to compare chemotherapy drugs, methotrexate (MTX), cyclophosphamide, cytarabine (Ara-C) and mercaptopurine (6mp) with nickel (Ni) and copper (Cu) complexes of thiosemicarbazone (TSCZ) in terms of their effects on the changes of Small Nucleolar RNA Host Gene 16(SNHG16) long non coding RNA (lncRNA) expression in the ALL cell line. Materials and Methods: this experimental study was conducted on various concentrations of chemotherapy drugs including MTX, CP, Ara-C, 6mp and Ni and Cu complexes of TSCZ. The Jurkat E6.1 cell lines were subjected to passage in different groups and times (24, 48, and 72h) and then treated with the chemotherapy drugs. After RNA extraction and cDNA synthesis, the SNHG16 gene expression was evaluated by Real-Time PCR, and the results were analyzed by the Rest software. Results: As the results indicated, within 24h, MTX (0.77, 0.72), CP (0.61, 0.7), ara-C (0.78, 0.87), Cu (0.91, 0.95) and Ni (0.94, 0.79) complexes as well as complex 1(0.73) and 2 (0.94) decreased the expression of SNHG16 gene significantly (P<0.001). Furthermore within 48h, under the influence of CP (0.86, 0.89) and   Ara-C (0.94, 0.97) as well as Cu (0.96) and Ni (0.98) complexes, the gene expression continued to decline(P<0.001).The greatest effect of chemotherapy drugs belonged to the combination of 1μM of ara-C and 5μM of 6mp.(P<0.001).       Conclusion: It was found that gene expression analysis is a feasible method to identify the pathways affected by the standard induction chemotherapy in ALL patients. This finding promotes the development of novel targeted drugs and biomarkers to categorize disease aggressiveness and evaluate treatment responses.
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