<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>