Dinkic Christine, Kruse Anja, Zygmunt Marek, Schuetz Florian, Brucker Janina, Rom Joachim, Sohn Christof, Fluhr Herbert
Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg, Germany.
Department of Gynecology and Obstetrics, University Hospital Greifswald, Greifswald, Germany.
Geburtshilfe Frauenheilkd. 2017 Oct;77(10):1104-1110. doi: 10.1055/s-0043-119289. Epub 2017 Oct 26.
Cancer patients have a higher risk for thromboembolic events compared to healthy individuals and are often treated with heparins. A beneficial effect of heparins on tumor patients above and beyond the classic anticoagulation effect has been reported, leading to an increased focus on the use of heparins in anticancer treatment. In recent years, it has become apparent that microenvironments greatly affect tumor development and can be a major source of tumor-promoting factors. Cytokines play an important role in tumor microenvironments, inducing carcinogenesis and influencing tumor progression by promoting angiogenesis, metastatic potential and immunosuppression. The possible interaction of heparins and cytokines could also have an effect on cancer cells.
This study investigated the effect of paclitaxel (PTX) combined with heparins on the vitality of endometrial cancer cells using viability and cytotoxicity assays. The study also examined whether treatment with paclitaxel and heparin influences cytokine secretion or expression.
Heparin treatment did not influence cell viability, and no influence of heparins in combination with paclitaxel was seen for the evaluated cancer cell lines HEC-1-A, KLE, RL 95-2 and AN3-CA compared to untreated cells. Secretion of the cytokines CCL5, CCL2 and IL-6 increased after paclitaxel treatment in several endometrial cancer cell lines, but no general effect on cytokine secretion was detected after heparin treatment. A significant decrease in CCL5 expression was only detected in KLE cells following treatment with heparin and paclitaxel, and an increase in the expression of CCL5 in RL 95-2 cells.
Further in-depth studies are needed to investigate the functions of cytokines CCL2, CCL5 and IL-6 in endometrial cancer cells treated with paclitaxel. Although no general effect on cytokine secretion was detected following heparin treatment, a selective modulatory impact could exist.
与健康个体相比，癌症患者发生血栓栓塞事件的风险更高，且常接受肝素治疗。已有报道称，肝素对肿瘤患者具有超越经典抗凝作用的有益效果，这使得人们更加关注肝素在抗癌治疗中的应用。近年来，很明显微环境对肿瘤发展有很大影响，并且可能是肿瘤促进因子的主要来源。细胞因子在肿瘤微环境中起重要作用，通过促进血管生成、转移潜能和免疫抑制来诱导致癌作用并影响肿瘤进展。肝素与细胞因子之间的可能相互作用也可能对癌细胞产生影响。
本研究使用活力和细胞毒性测定法，研究紫杉醇（PTX）联合肝素对子宫内膜癌细胞活力的影响。该研究还考察了紫杉醇和肝素治疗是否会影响细胞因子的分泌或表达。
肝素治疗不影响细胞活力，与未处理的细胞相比，在所评估的癌细胞系HEC-1-A、KLE、RL 95-2和AN3-CA中，未观察到肝素与紫杉醇联合使用有影响。在几种子宫内膜癌细胞系中，紫杉醇治疗后细胞因子CCL5、CCL2和IL-6的分泌增加，但肝素治疗后未检测到对细胞因子分泌的总体影响。仅在肝素和紫杉醇处理后的KLE细胞中检测到CCL5表达显著降低，而在RL 95-2细胞中CCL5表达增加。
需要进一步深入研究以探讨细胞因子CCL2、CCL5和IL-6在用紫杉醇治疗的子宫内膜癌细胞中的功能。虽然肝素治疗后未检测到对细胞因子分泌的总体影响，但可能存在选择性调节作用。
