ABSTRACT
<p><b>OBJECTIVE</b>To study the in vivo interference effects of vascular endothelial growth factor (VEGF) short hairpin RNA (shRNA) on xenografts of drug-resistant tongue cancer cells.</p><p><b>METHODS</b>Drug-resistant tongue caner cells Tca/Cisplatin (DDP) were injected subcutaneously into nude mice to establish xenograft models, which were randomly divided into non-transfected group, mock control group, control group transfected with scrambled sequence plasmid, interference group transfected with VEGF-shRNA expression plasmid. Liposome-mediated plasmid transfection was done in the latter three groups every three days. Xenografts were observed and tumor growth curve was measured. After the 10th transfection, tumors were anatomized and weigh. Microvessel density was detected by immunohistochemical staining. In situ hybridization assay was used to test VEGF mRNA, and immunohistochemistry to test VEGF, P-glycoprotein (P-gp), B cell lymphoma/leukemia-2 (bcl-2) and extracellular signal-regultaed kinase 2 (ERK-2) protein.</p><p><b>RESULTS</b>Tumor growth in VEGF-shRNA interference group was significantly slow. Tumor weight was (0.4781 ± 0.0860) g, microvessel density (7.35 ± 1.31)/view, VEGF mRNA (0.0767 ± 0.0234), VEGF protein (0.1301 ± 0.0433), P-gp (0.1517 ± 0.0184), bcl-2 (0.1218 ± 0.0251) and ERK-2 protein (0.1178 ± 0.0291) in VEGF-shRNA interference group; all of them were less than those in the other three groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Inhibition targeting VEGF may become a potential therapy for drug-resistant tongue cancer.</p>
Subject(s)
Animals , Female , Humans , Mice , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Carcinoma, Squamous Cell , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Cisplatin , Pharmacology , Drug Resistance, Neoplasm , Mice, Inbred BALB C , Mice, Nude , Microvessels , Pathology , Mitogen-Activated Protein Kinase 1 , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , RNA Interference , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , Random Allocation , Tongue Neoplasms , Metabolism , Pathology , Transfection , Tumor Burden , Vascular Endothelial Growth Factor A , Genetics , Metabolism , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To determine the effect of tyrosine kinase A (TrkA) and vascular endothelial growth factor receptor 2 (VEGFR2) in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC).</p><p><b>METHODS</b>The expression of TrkA and VEGFR2 were detected by immunohistochemical staining in 47 cases of SACC of salivary glands. Clinical data were reviewed by multivariate prognostic analysis.</p><p><b>RESULTS</b>The positive rate of TrkA and VEGFR2 in SACC was 87.23% (41/47) and 85.11% (40/47) respectively. Express of TrkA and VEGFR2 in perineural invasion and recurrence group were higher than non-perineural invasion and non-recurrence group. Significant difference was found in microvessel density (MVD) and VEGFR2 expression within different groups (P < 0.05). MVD in perineural invasion group (25.14 +/- 2.83) was significantly higher than that in none perineural invasion group (18.81 +/- 1.33) (P < 0.05). MVD in recurrence or metastasis group (26.58 +/- 2.38) was significantly higher than that (19.06 +/- 1.39) in none recurrence nor metastasis group (P < 0.05).</p><p><b>CONCLUSION</b>Positive correlation between expression of TrkA, VEGFR2 and nerve invasion and vessel metastasis of SACC indicate that TrkA and VEGFR2 play important roles in the invasion and metastasis of SACC. It is possible that TrkA and VEGFR2 could be an aid for evaluating the prognosis of SACC patients.</p>
Subject(s)
Humans , Carcinoma, Adenoid Cystic , Metabolism , Pathology , Neoplasm Metastasis , Neoplasm Recurrence, Local , Receptor, trkA , Metabolism , Salivary Gland Neoplasms , Metabolism , Pathology , Vascular Endothelial Growth Factor Receptor-2ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of angiogenesis inhibitor and its combine with chemical drug in suppressing the growth of adenoid cystic carcinoma (ACC).</p><p><b>METHODS</b>Acc-M cells were inoculated subcutaneous into BABL/C nu/nu mice. The mice were divided into control, different dose of TNP-470 treatment groups, 5-Fu treatment group and TNP-470 plus 5-Fu treatment group. Treatments were given 48 hours after inoculation. The mice were sacrificed on the 22nd day and excised tumors were weighted. Tumors were also investigated by immunohistochemistry and ultrastructural observations.</p><p><b>RESULTS</b>TNP-470 100 mg/kg/qod efficiently inhibited the growth of Acc-M tumors. TNP-470 30 mg/kg/qod combined with 50 mg/kg/week 5-Fu also resulted in significant growth inhibit of the tumors. TNP-470 suppressed tumor growth by inhibiting neovascularization, therefore inducing apoptosis of Acc-M cells. All experimental groups had different degrees of VEGF and bFGF express.</p><p><b>CONCLUSION</b>Since ACC is a slow developing tumor, blood supply is not so sufficient as sarcomas. Angiogensis inhibitor may inhibit its growth in high dosage. Combining medium dosage of angiogensis inhibitor with chemical drug may have synergistic result in inhibiting ACC growth.</p>