Effects of WD‑3 on tumor growth and the expression of integrin αvβ3 and ERK1/2 in mice bearing human gastric cancer using the 18F‑RGD PET/CT imaging system

Chunhui Jin, Bao-Nan Zhang, Zhipeng Wei, Bo Ma, Qi Pan, Pingping Hu
Molecular Medicine Reports 2017, 16 (6): 9295-9300
Activation of the vitronectin receptor αvβ3 and the phosphorylation of extracellular signal‑regulated kinase (ERK)1/2 are critical events during tumor development and progression. The aim of the present study was to investigate the effects of WD‑3, a formula used in traditional Chinese medicine, on integrin αvβ3 and ERK1/2 expression in vivo using a nude mouse‑human gastric cancer xenograft model combined with non‑invasive, real‑time 18F‑Arg‑Gly‑Asp (RGD) positron emission tomography (PET)/computerized tomography (CT) imaging methods. SGC‑7901 human gastric cancer cells were subcutaneously injected into BALB/c nude mice. Following tumor development, animals were randomly assigned into the following 4 groups (n=6 mice/group): Control group (CG), Chinese medicine group (CMG), Western medicine group (WMG) and Chinese and Western medicine combination group (CMG + WMG). Mice in the CG and CMG received daily intragastric injections of 0.5 ml saline and 0.5 ml WD‑3, respectively. Mice in the WMG received an intravenous injection of albumin‑bound paclitaxel (25 mg/kg) on days 0, 2 and 4 Mice in the CMG + WMG received combination therapy of WD‑3 and albumin‑bound paclitaxel. Tumor growth was monitored using standard caliper technique and via PET imaging. 18F‑RGD PET/CT analysis was performed on days 3, 7, 18 and 24 following drug administration. Radioactivity uptake was measured and expressed as the percentage of injected dose (ID) per tissue weight (%ID/g) ​​ and the standardized uptake value (SUV). Animals were sacrificed at 30 days following treatment and tumor weight was measured. Immunohistochemistry was used to detect the expression of phosphorylated (p)‑ERK1/2 protein in tumor tissue samples. No statistically significant differences were observed in %ID/g and SUV among the various groups prior to treatment. At the end of treatment, mice in the CMG, WMG and CMG + WMG exhibited significantly reduced tumor mass when compared with mice in the CG. In addition, mice in the CMG and CMG + WMG demonstrated reduced %ID/g and SUV when compared with mice in the CG. Conversely, mice in the WMG exhibited no significant difference in %ID/g and SUV compared with the CG. Furthermore, p‑ERK1/2 expression was significantly reduced in mice from all treatment groups when compared with those in the CG. The results of the present study suggest that the traditional Chinese formula WD‑3 may inhibit gastric tumor growth, potentially via the downregulation of integrin αvβ3 and the inhibition of ERK1/2 phosphorylation in vivo.

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