Oncolytic virotherapy is emerging as an important agent in
cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual
cancer-selective anti-
tumor recombinant adenovirus. In this study,
crystal violet staining and WST-1 assays showed that Ad-VT has a significant
tumor killing effect in a time and dose dependent manner. The combination of Ad-VT (10 MOI) and
gemcitabine (10 nM) significantly inhibited NCI-H226 cells, but did not increase the killing effect of
gemcitabine on human normal bronchial epithelial cells BEAS-2B. Hoechst,
JC-1 and
Annexin V experiments demonstrated that the combination of Ad-VT and
gemcitabine mainly inhibited NCI-H226 cell proliferation by inducing apoptosis (mitochondrial pathway). The combination also significantly inhibited the migration and invasion abilities of NCI-H226 cells. In vivo, Ad-VT in combination with low-dose
gemcitabine could effectively inhibit
tumor growth and prolong survival of mice. Ad-VT has the characteristics of
tumor-selective replication and killing, in vitro and in vivo. The combined application of Ad-VT and
gemcitabine has a synergistic effect, which can increase the anti-
tumor effect and reduce the toxicity of
chemotherapy drugs, indicating that Ad-VT has a potential clinical value in the treatment of lung
squamous cell carcinoma.