Kilic Arman, Schuchert Matthew J, Luketich James D, Landreneau Rodney J, El-Hefnawy Talal
Heart, Lung, and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15232, USA.
J Surg Res. 2009 Jun 1;154(1):9-12. doi: 10.1016/j.jss.2008.05.022. Epub 2008 Jun 20.
Signal pathway inhibitors (SPI) are designed to act synergistically with conventional cytotoxic drugs to control cancer progression. The objective of this study was to evaluate the effect of various SPI, both alone and in combination with cisplatin, on three different non-small cell lung cancer (NSCLC) cell lines.
Cell lines (A549, 201T, 273T) representing NSCLC were treated for 72 h in the presence or absence of inhibitors to PI3K (LY-294002; Tocris Bioscience, Ellisville, MO), BCL-2 (Gossypol; Sigma-Aldrich, St. Louis, MO), Cox-2 (NS-398 [Sigma-Aldrich] or Celecoxib [Pfizer]), MAPK (U0126 [Sigma-Aldrich]), and EGFR (Iressa; AstraZeneca, Macclesfield, United Kingdom) both alone and in combination with 10 or 30 mum cisplatin (Sigma-Aldrich) (18 possible regimens for each cell line). MTT assay (Trevigen, Gaithersburg, MD) was used to measure cytotoxicity. Controls were represented by cells with either a pure culture medium (monotherapy regimen control) or culture medium with the corresponding dose of cisplatin (combination regimen control). Unpaired t-test was used to classify response to therapy as highly sensitive (P < 0.01), sensitive (0.01 < or = P < 0.05), or resistant (P > or = 0.05). Concordance was defined as a similar response category between cell lines.
The concordance rate was 50% between each of the three cell lines when SPI were used as monotherapy. In combination regimens, the concordance rates were 33% (A549 and 273T), 17% (A549 and 201T), and 75% (273T and 201T). The 273T cells were most susceptible to therapy, having 11 (61%) highly sensitive responses, whereas A549 cells were least susceptible with 14 (78%) resistant responses.
There is a substantial degree of variability between NSCLC cell lines in response to SPI, both alone and in combination with cisplatin.
信号通路抑制剂（SPI）旨在与传统细胞毒性药物协同作用以控制癌症进展。本研究的目的是评估各种SPI单独及与顺铂联合使用时，对三种不同的非小细胞肺癌（NSCLC）细胞系的作用。
代表NSCLC的细胞系（A549、201T、273T）在存在或不存在PI3K抑制剂（LY - 294002；Tocris Bioscience，埃利斯维尔，密苏里州）、BCL - 2抑制剂（棉酚；Sigma - Aldrich，圣路易斯，密苏里州）、Cox - 2抑制剂（NS - 398 [Sigma - Aldrich]或塞来昔布[辉瑞]）、MAPK抑制剂（U0126 [Sigma - Aldrich]）和EGFR抑制剂（易瑞沙；阿斯利康，麦克尔斯菲尔德，英国）的情况下处理72小时，单独及与10或30 μmol顺铂（Sigma - Aldrich）联合使用（每个细胞系有18种可能的方案）。采用MTT法（Trevigen，盖瑟斯堡，马里兰州）测量细胞毒性。对照组为纯培养基中的细胞（单一疗法方案对照）或含有相应剂量顺铂的培养基中的细胞（联合疗法方案对照）。采用非配对t检验将治疗反应分类为高度敏感（P < 0.01）、敏感（0.01≤P < 0.05）或耐药（P≥0.05）。一致性定义为细胞系之间相似的反应类别。
当SPI作为单一疗法使用时，三种细胞系两两之间的一致率为50%。在联合方案中，一致率分别为33%（A549和273T）、17%（A549和201T）和75%（273T和201T）。273T细胞对治疗最敏感，有11种（61%）高度敏感反应，而A549细胞最不敏感，有14种（78%）耐药反应。
NSCLC细胞系对SPI单独及与顺铂联合使用的反应存在很大程度的变异性。
