Department of Otorhinolaryngology, University of Schleswig-Holstein, Lübeck, Germany.
Anticancer Res. 2013 Jun;33(6):2481-9.
Radiation and systemic chemotherapy are standard treatment strategies for advanced or metastatic head and neck cancer. However, little is known about the implications and changes in the tumor microenvironment, including the T-helper (TH)1/TH2 balance in response to these treatment regimens. The aim of the current study was to unravel the effects of chemotherapeutic drugs and radiation on cytokine changes.
In this study, the effect of radiation and chemotherapeutic treatment (5-fluorouracil and cisplatin) on eight cell lines was determined. Before and after exposure, cytokine levels in culture supernatants of cell lines were evaluated using the Bio-Plex Assay (Bio-Rad) and the Human TH1/TH2 Cytometric Bead Array (Becton Dickinson). Results were correlated with parallel measurements for cellular proliferation assessed by cytotoxicity assay.
Seven out of eight cell lines of primary tumors or metastases demonstrated an enhanced level of the cytokines interleukin (IL)-1β, IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-α (TNF-α), after sub-lethal radiation doses. Under treatment with low concentrations of 5-fluorouracil and cisplatin, all examined cell lines showed an increasing secretion of the cytokines IL-6 and G-CSF. In contrast, sub-lethal doses of both cytostatic drugs revealed a dose-dependent decrease in secretion IL-1β. Regarding GM-CSF and TNF-α, we demonstrated an increase in secretion by the primary tumors under low doses of 5-fluorouracil and cisplatin, whereas the metastases showed a sharp drop of GM-CSF and TNF-α secretion. Chemotherapeutic treatment led to no changes of the IL-8 cytokine profile.
The results suggest complex cytokine changes of the tumor microenvironment and more aberrant expression profiles under treatment with radiation and the chemotherapeutic drugs 5-fluorouracil and cisplatin.
放疗和全身化疗是治疗晚期或转移性头颈部癌症的标准治疗策略。然而，对于这些治疗方案引起的肿瘤微环境变化，包括 T 辅助细胞（TH）1/TH2 平衡，我们知之甚少。本研究旨在阐明化疗药物和放疗对细胞因子变化的影响。
本研究测定了放疗和化疗（5-氟尿嘧啶和顺铂）对 8 种细胞系的影响。在暴露前后，使用 Bio-Plex 检测试剂盒（Bio-Rad）和人 TH1/TH2 细胞因子流式微球检测试剂盒（Becton Dickinson）评估细胞系培养上清液中的细胞因子水平。结果与细胞毒性检测评估的细胞增殖平行测量相关联。
7 种原发肿瘤或转移灶的细胞系在亚致死剂量的放疗后，白细胞介素（IL）-1β、IL-6、IL-8、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子-α（TNF-α）的细胞因子水平升高。低浓度 5-氟尿嘧啶和顺铂治疗下，所有检测的细胞系均表现出 IL-6 和 G-CSF 分泌增加。相反，两种细胞毒药物的亚致死剂量均显示 IL-1β 分泌呈剂量依赖性下降。关于 GM-CSF 和 TNF-α，我们发现在低剂量的 5-氟尿嘧啶和顺铂下，原发肿瘤的分泌增加，而转移瘤则显示 GM-CSF 和 TNF-α 分泌急剧下降。化疗治疗未导致细胞因子 IL-8 谱的变化。
结果表明，放疗和化疗药物 5-氟尿嘧啶和顺铂治疗后，肿瘤微环境中的细胞因子发生复杂变化，表达谱更异常。
