The anti-tumor effect of combined treatment with arsenic trioxide and interferone-α on transplanted murine Lewis lung carcinoma

In the present study, we expected the anti-tumor effect by combined treatment of arsenic trioxide and interferon (IFN)-${\alpha}$ on murine Lewis lung carcinoma (LL2) cells through in vivo study. As a experimental model, LL2 cells ($1{\times}10^{6}$/mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached $100mm^3$, mice were treated with 1 mg/kg arsenic trioxide, 50000 IU IFN-${\alpha}$, or arsenic trioxide and IFN-${\alpha}$. The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN-${\alpha}$. In arsenic trioxide and IFN-${\alpha}$ treated group, apoptotic index was reached a peak valve at 48 hr after the treatment and it was restored to approximately the control level at 8 days. Also, positive signals of Bax and Bad were increased at 48 to 96 hr and decreased at 8 day. Whereas, positive cells of Bcl-2 were steadily decreased at 12 to 48 hr and restored to the background level at 8 days. Our data showed that immunoreactivity of Bcl-2 was decreased at 12 to 48 hr, while positive signals of Bax and Bad were increased in accordance with apoptotic index at these times. In conclusion, our results suggest that the combined treatment with arsenic trioxide and IFN-${\alpha}$ significantly inhibited the growth of LL2 tumor cells and induced apoptosis through the up and down-regulation of Bcl-2 gene family.