Anti-nasopharyngeal carcinoma effect in vivo and in vitro of Avastin and adenovirus-thymidine kinase suicide gene / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the effect of Avastin and adenovirus-thymidine kinase/ Ganciclovir (Ad-TK/GCV) suicide gene system on nasopharyngeal carcinoma in vivo and in vitro.</p><p><b>METHODS</b>The expression of vascular endothelial growth factor (VEGF) by CNE1 cell line was detected by VEGF ELISA. The effect of Avastin and Ad-TK/GCV on CNE1 cell was detected by methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and Hoechst 33342 staining were adopted to explore the killing mechanism of Ad-TK/GCV. The nude mice models of CNE1 cell xenografts were established. After intra-tumoral injection of PBS, Avastin, Ad-TK/GCV, Ad-Lac-Z/GCV and Ad-TK/GCV + Avastin, tumor volume was measured and tumor inhibitory rate was calculated. Then the tumors were removed and subjected to histological examination.</p><p><b>RESULTS</b>CNE1 cells could produce VEGF. Avastin had no direct effect on CNE1 cells. The killing effect of Ad-TK/GCV increased with the increase of Ad-TK multiple of infection and the prodrug concentration, which was enhanced by the existence of bystander effect. Compared with control group, the death cell rate (P = 0.000) and apoptosis cell rate (P = 0.000) had significant difference. The study in vivo showed the tumors treated with Avastin, Ad-TK/GCV and Ad-TK/GCV + Avastin grew slowly compared with control. Tumor volume of treated groups was significantly smaller than that of control (all P < 0.05 or P = 0.000). Tumor weight of treated groups was significantly lower than that of control (all P = 0.000). The histological examination showed local necrosis in Ad-TK/GCV group and Ad-TK/GCV + Avastin group, poor angiogenesis in Avastin group and Ad-TK/GCV + Avastin group.</p><p><b>CONCLUSIONS</b>Avastin had no direct effect on CNE1 cells in vitro. Ad-TK/GCV suicide gene system killed NPC cells by inducing cell necrosis and apoptosis, which could be enhanced by the existence of bystander effect. Avastin and Ad-TK/GCV suicide gene system could inhibit the growth of NPC CNE1 cell xenografts. Combination therapy had a synergic effect.</p>