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基于小细胞肺癌细胞的传感器研究及其在抗癌药物化疗效果快速评估中的应用。

Study of small-cell lung cancer cell-based sensor and its applications in chemotherapy effects rapid evaluation for anticancer drugs.

机构信息

Zhejiang Agriculture & Forestry University, Hangzhou 311300, China.

Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou 310022, China.

出版信息

Biosens Bioelectron. 2017 Nov 15;97:184-195. doi: 10.1016/j.bios.2017.05.050. Epub 2017 May 31.

DOI:10.1016/j.bios.2017.05.050
PMID:28599178
Abstract

Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening.

摘要

小细胞肺癌(SCLC)是一种与吸烟有关的癌症疾病。尽管临床生存率有所提高,但 SCLC 的预后仍然非常差。顺铂(DDP)是 SCLC 的一线化疗药物,但二线化疗药物的选择尚不清楚。本文提出了一种基于 SCLC 细胞的传感器,并研究了其在评估抗癌药物化疗效果方面的应用。将肺腺癌细胞(LTEP-P)和 DDP 耐药肺腺癌细胞(LTEP-P/DDP-1.0)培养在碳丝网印刷电极(CSPE)上,以制备集成的基于细胞的传感器。选择几种化疗抗癌药物,包括顺铂、异环磷酰胺、吉西他滨、紫杉醇、多西他赛、长春瑞滨、依托泊苷、喜树碱和拓扑替康,作为实验化学品。MTT 试验用于评估 LTEP-P 和 LTEP-P/DDP-1.0 细胞系中化疗药物的作用。通过双层级联随机共振(DCSR)测量和处理针对抗肿瘤化学品的电细胞-基底阻抗传感(ECIS)响应。不同浓度顺铂溶液的测量结果表明,LTEP-P 细胞传感器具有对顺铂和拓扑替康进行定量分析的能力。还可以区分顺铂及其混合物。结果表明,LTEP-P 细胞传感器能够灵敏地评估化疗药物对 SCLC 细胞的凋亡作用。根据 MTT 试验结果,LTEP-P/DDP-1.0 细胞传感器的响应表明,与其他药物相比,吉西他滨、长春瑞滨和喜树碱是临床顺铂治疗后理想的二线药物。这项工作为 SCLC 二线临床化疗药物筛选提供了一种新方法。

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