Systemic inhibition of tumor growth by soluble Flk-1 gene therapy combined with cisplatin

Abstract

Soluble Flk-1, a soluble vascular endothelial growth factor (VEGF) receptor, is a potent inhibitor of angiogenesis, which could restrain growth and metastasis of some experimental tumors. However, antiangiogenic agents alone cannot eradicate tumor completely, and should be combined with other therapy to enhance their effects. In this study, we evaluated the antitumor activity of the combination therapy in the immunocompetent BALB/c mice bearing H22 hepatoma and Meth A fibrosarcoma, respectively. Mice were treated with either msFlk-1 i.m. at 100 mg/mouse once every 3 days for four times from day 3 after the tumor cell injection, cisplatin cycled twice (2 mg/kg i.p. on days 4 and 11 after the tumor cell inoculation), or both agents together. Tumor growth and survival time were continually observed. Antiangiogenesis in vivo was determined by CD31 immunohistochemistry. Assessment of apoptotic cells and histological analysis was also conducted in tumor tissues. Our results showed that the combination therapy could evidently improve antitumor efficacy, including tumor growth suppression, mice survival prolongation, tumor cell apoptosis augmentation as well as neovascularization inhibition as compared with controls, without serious adverse effects. Our data suggest that the combination of DDP with msFlk-1 is more effective to suppress tumor growth in mice than either agent alone, and this combination regimen showed its potential for future clinical application.

Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells

“…To conform the role of FPR1 in HCC progression by in vivo experiments using murine cancer cell lines in immunocompetent mice, we examined the effect of FPR1 tumorigenicity in H22 tumor model of BALB/c mice following the method described by another group. 26 We show that FPR1-shRNA had similar antitumor effects in immunocompetent mice shown in immunocompromised mice with human cell line (Fig. S6A, B and C).…”

The corpora lutea proangiogenic state of VEGF system components is turned to antiangiogenic at the later phase of the oestrous cycle in cows

“…The soluble forms of the VEGF receptors bind to the ligand and block their angiogenic action (Kaczmarek et al, 2005). Cancer therapy studies have shown that an increase in the expression of sVEGFR1 (Owen et al, 2012) or sVEGFR2 (Wang et al, 2006;Szentirmai et al, 2008) reduce tumour cell proliferation and increase apoptosis (Szentirmai et al, 2008), which is associated with a reduction in blood flow to the tumour tissues. In the present study, mRNA expression of VEGFR2 on days 4 and 6 (CL formation) of the cycle was at least eightfold higher than that Figure 2 Changes in the ratio of mRNA expression for angiogenic (VEGF120a, VEGFR1 and VEGFR2) and antiangiogenic (VEGF120b, sVEGFR1 and sVEGFR2) VEGF system components in the corpus luteum during the oestrous cycle.…”

Inhibitory effect of Bifidobacterium infantis-mediated sKDR prokaryotic expression system on angiogenesis and growth of Lewis lung cancer in mice

“…Thus, sKDR can bind with VEGF and compete with normal VEGFR-2 and can function as dominant negative by forming inactive heterodimers with membrane-spanning VEGF receptors [12,38]. To date, many studies have proven that the specific binding of sKDR with VEGF could significantly inhibit the blood vessel formation in tumor tissue, thereby inhibiting the growth, proliferation and migration of tumor [15,23,31,38]. …”

“…The soluble kinase insert domain receptor (sKDR) is a soluble form of the extramembrane part of VEGFR2 [14]. It has the same high affinity for VEGF but does not induce angiogenesis [15]. Thus, the delivery of sKDR to tumor tissues inhibits the formation of new blood vessels in the tumor tissues and has an anti-tumor effect [6,16].…”