Vesicular Stomatitis Virus In Combination With Gemcitabine Treatment Of Lung Cancer Experimental Research

Lung cancer is the leading cause of cancer related death in both males and females. The therapeutic improvement on traditional surgery, chemotherapy and radiotherapy seems to have reached a plateau. Efforts are continuing to develop new and less toxic therapeutic approaches for the treatment of lung cancer.Vesicular Stomatitis Virus (VSV) has been shown to rapidly replicate in vitro and selectively kill a variety of tumor cell lines even in the presence of interferon. It exhibits the antitumor activity in both human tumor xenografts in nude mice and syngeneic tumors in the immunocompetent mice. Gemcitabine is a new deoxycytidine analogue, which inhibits DNA synthesis. It has been frequently used to treat non-small cell lung cancer patients. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro and in vivo.The lung cancer cells treated with VSV plus gemcitabine displayed the marked cytopathic effect observed by phase contrast microscopy, apparent increase in the number of sub-G1 cells of propidium-iodide-stained nuclei analyzed by flow cytometry and the increased number in propidium-iodide-stained condensed nuclei and nuclear fragmentation, compared with treatment with VSV or gemcitabine alone. In addition, a ladder-like pattern of DNA fragments is consistent with internucleosomal DNA fragmentation. The combined treatment with VSV plus gemcitabine induced the synergistic antitumor activity with complete regression of the established lung cancer in both A549 and LLC lung cancer models, and augmented the induction of apoptosis in lung cancer cells in vivo. Takentogether, the present study suggest that the combined treatment with VSV plus gemcitabine may augment the induction of apoptosis in lung cancer cells in vitro and in vivo, and that the augmented antitumor activity in vivo may result from synergistic induction of apoptosis in lung cancer cells. The present findings may be of importance to the further exploration of the potentialapplication of this combined approach in the treatment of lung cancer.