Abstract
To explore the inhibiting effect and mechanism of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts in nude mice. A total of 24 nude mice with subcutaneous xenografts of the A549 cell line were established and divided into 4 groups when the maximal diameters of tumors became 1 cm: control group, Endostar group, cryoablation group and combination group (Endostar concomitant with cryoablation). The nude mice were sacrificed after 21-days treatment, tumour tissues were removed to measure their volume, in situ test of TdT-mediated dUTP nick end labeling (TUNEL) was adopted to determine the cellular apoptosis around freezing injury zones, and immunohistochemical SP test was applied for the detection of micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression levels. At 21-days after treatment, the growth velocities of control group, Endostar group, cryoablation group and combination group were 236.7 ± 51.2%, 220.0 ± 30.6%, 159.5 ± 29.3% and 103.3 ± 25.5% (P<0.01), while cellular apoptosis rates of tumors were 21.7 ± 2.34%, (22.17 ± 1.47)%, 38.3 ± 1.37% and 49.2 ± 1.72%, (P<0.01), respectively, according to the immunohistochemical test. MVD and VEGF expression levels in the combination group were both lower than in other groups (P<0.01), also being positively related (r=0.925, P<0.01). Endostar can significantly improve the inhibitory effects of cryoablation on xenografts of lung adenocarcinoma A549, and the mechanism is probably associated with its function as an inhibitor of tumour neo-angiogenesis through down-regulating VEGF expression.
Highlights
Recombinant Human Endostatin Injection, named as Endostar Injection, is a new targeted drug developed independently by Chinese researchers, which can strongly inhibit tumor angiogenesis (Folkman, 2006) and has certain effect on middle and advanced non-small cell lung cancer (NSCLC) when concomitant with chemotherapies (Wang et al, 2005; Fei et al, 2013; Yan et al, 2013; Liu et al, 2013; Lu et al, 2013; Yin et al, 2013)
Endostar is a new human endostatin independently created and angiogenesis via inhibiting the activation, proliferation and metastasis of vascular endothelium; improve the transient “normalization” of tumor cells to keep them in developed by Chinese scholars through modifying the amino acid sequence of endostatin, which has favorable anti-tumor angiogenesis, with its objective effective dormant state, so as to induce the apoptosis and promote the sensitivity of tumor cells on physical and chemical damages (Mauceri et al, 1998; Lee et al, 2000)
This rate being 3%~5% in single use, and has synergistic and favorable clinical effects when concomitant with chemotherapy in treating advanced NSCLC (Wang et study revealed that micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression in residual tumor cells decreased significantly in combination group, predicating that Endostar could inhibit tumor angiogenesis al., 2005)
Summary
Recombinant Human Endostatin Injection, named as Endostar Injection, is a new targeted drug developed independently by Chinese researchers, which can strongly inhibit tumor angiogenesis (Folkman, 2006) and has certain effect on middle and advanced non-small cell lung cancer (NSCLC) when concomitant with chemotherapies (Wang et al, 2005; Fei et al, 2013; Yan et al, 2013; Liu et al, 2013; Lu et al, 2013; Yin et al, 2013). It has been included in Chinese Version of Clinical Practice Guideline of Non-small Cell Lung Cancer of National Comprehensive Cancer Network (NCCN). This study, through establishing the nude mice model of xenograft of human lung adeno-carcinoma A549, observed the anti-tumor effect of Endostar concomitant with cryoablation, so as to further investigate its mechanism, providing references for clinical treatment of middle and advanced NSCLC
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