Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China.
Department of Radiology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8103-8109. doi: 10.3892/mmr.2017.7589. Epub 2017 Sep 22.
Cytostatic antineoplastic drugs are considered carcinogenic and mutagenic risk factors for health workers who are occupationally exposed to them; however, the molecular mechanisms underlying these effects remain to be elucidated. Therefore, the present study aimed to investigate the underlying mechanisms of antineoplastic drugs‑induced apoptosis of peripheral blood lymphocytes (PBLs) obtained from oncology nurses handling antineoplastic drugs. A microRNA (miRNA/miR) polymerase chain reaction (PCR) array was performed to analyze the expression levels of miRNAs in the PBLs from 3 trained nurses occupationally exposed to antineoplastic drugs. The effects of miR‑34a on cell proliferation and apoptosis in temozolomide (TMZ) treated PBLs were analyzed by cell counting kit‑8 and flow cytometry assays. The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein, caspase‑3 and caspase‑9 were determined by western blot analysis, and miR‑34a expression levels were detected using quantitative reverse transcription‑PCR. The results of the present study demonstrated that miR‑34a was significantly upregulated in oncology nurses that were occupationally exposed to antineoplastic drugs. In addition, TMZ suppressed cell proliferation and induced apoptosis, by promoting the expression of miR‑34a, in a dose‑dependent manner, and also inhibited the expression of Bcl‑2. Furthermore, knockdown of miR‑34a was able to reverse the reduction of cell proliferation and promotion of apoptosis induced by TMZ in PBLs. Together, these results indicated that abnormal expression of miR‑34a may be considered a diagnostic marker in nurses occupationally exposed to antineoplastic drugs.
细胞抑制剂抗肿瘤药物被认为是职业接触这些药物的卫生保健工作者致癌和致突变的危险因素；然而，这些作用的分子机制仍有待阐明。因此，本研究旨在探讨抗肿瘤药物诱导的接触抗肿瘤药物的肿瘤护士外周血淋巴细胞（PBL）凋亡的潜在机制。通过微 RNA（miRNA/miR）聚合酶链反应（PCR）阵列分析 3 名职业接触抗肿瘤药物的训练有素的护士 PBL 中 miRNA 的表达水平。通过细胞计数试剂盒-8 和流式细胞术分析 miR-34a 对替莫唑胺（TMZ）处理的 PBL 中细胞增殖和凋亡的影响。通过 Western blot 分析测定 B 细胞淋巴瘤 2（Bcl-2）、Bcl-2 相关 X 蛋白、半胱氨酸天冬氨酸蛋白酶-3 和半胱氨酸天冬氨酸蛋白酶-9 的蛋白表达水平，并通过定量逆转录-PCR 检测 miR-34a 的表达水平。本研究结果表明，职业接触抗肿瘤药物的肿瘤护士 miR-34a 表达明显上调。此外，TMZ 通过促进 miR-34a 的表达，呈剂量依赖性抑制细胞增殖并诱导细胞凋亡，还抑制 Bcl-2 的表达。此外，miR-34a 的敲低能够逆转 TMZ 在 PBL 中诱导的细胞增殖减少和凋亡促进。综上所述，这些结果表明异常表达的 miR-34a 可被视为职业接触抗肿瘤药物的护士的诊断标志物。
