Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Highlights

  • Endometrial cancer is the most common gynecologic malignancy with a peak incidence between the ages of 55 and 65 years [1]

  • 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

  • Further in-depth studies are needed to investigate the functions of cytokines CCL2, CCL5 and IL-6 in endometrial cancer cells treated with paclitaxel

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Summary

Introduction

Endometrial cancer is the most common gynecologic malignancy with a peak incidence between the ages of 55 and 65 years [1]. Around 142 000 women are affected by endometrial cancer worldwide every year [1]. Endometrial cancer is frequently diagnosed at an early stage as affected women often present with abnormal vaginal bleeding. Different therapeutic modalities including radiotherapy and surgery and systemic therapies such as chemotherapy and hormone therapy are used to treat recurrent endometrial cancer [3]. Clinical trials evaluating chemotherapy regimens in patients with endometrial cancer include combinations of doxorubicin and cisplatin, cyclophosphamide or paclitaxel and carboplatin, most of them administered in a palliative setting [3]. These systemic treatment options are often accompanied by high toxicity. The possible interaction of heparins and cytokines could have an effect on cancer cells

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