Inhibitory Effect of Endostar on Lymphangiogenesis in Non-small Cell Lung Cancer and Its Effect on Circulating Tumor Cells

Abstract

Background and objective It is unclear how could endostatin effect tumor lymphangiogenesis? The aim of this study is to explore inhibitory effect of recombinant human endostatin injection (endostar) on lymphangiogenesis in non-small cell lung cancer (NSCLC) tissue and its effect on circulating tumor cells (CTC) in peripheral blood. Methods Tumor-bearing model nude mice were divided into eight groups randomly (n=7), including control group, cisplatin group, several concentration endostar groups and endostar plus cisplatin groups. Continuous administration of Endostar for two weeks, observed one week after the end of administration. Using HE staining and immunohistochemical staining to diagnose the tumor tissue and suspect metastasis lymph nodes, detected vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3 expression level and microlymphatic vessel density (MLVD) of tumor tissue. Enrichment of circulating tumor cells in peripheral blood used immunomagnetic negative selection strategy, used immunofluorescence staining to diagnose and count CTCs. Results Microlymphatic vessel density and the positive expression rate of VEGF-C, VEGF-D, VEGFR-3 in three endostar groups and three endostar plus cisplatin groups were significantly less than those in control group and cisplatin group. Microlymphatic vessel density and the positive expression rate of VEGF-C, VEGF-D, VEGFR-3 in endostar plus cisplatin group and endostar group with high endostar concentration were significantly less than those with low endostar concentration; There was a significant positive correlation between microlymphatic vessel density and the positive expression rate of VEGF-C, VEGF-D, VEGFR-3. The number of circulating tumor cells in endostar plus cisplatin groups were significantly less than that of endostar or cisplatin alone. Conclusion Endostar could inhibit tumor lymphangiogenesis and reduce tumor cells into the bloodstream through the lymphatic. Inhibitory effect concerned with drug concentrationwith a dose-dependant.

Keywords

• Recombinant human endostatin injection
• Tumor-bearing model
• Microlymphatic vessel density
• Positive expression rate
• Circulating tumor cells