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Combined Effect with Arsenic Trioxide and Interferon-α on Transplanted Murine Lewis Lung Carcinoma
Deug-Log Seo,Je-Hoon Yang,Chung-Kil Won,Chung-Boo Kang,Kyu-Woan Cho,Mi-Hyun Ha,Soo-Dong Kwak,Phil-Ok Koh 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.3
The aim of this work was to study the anti-tumor effect by combined treatment of arsenic trioxide and interferon-α (IFN-α) in mice injected murine Lewis lung carcinoma (LL2) cells. As a experimental model, LL2 cells (1×10⁶/mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached about 100 ㎣, mice were treated with 1 ㎎/㎏ arsenic trioxide, 50,000 IU IFN-α, or arsenic trioxide plus IFN-α, respectively. The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN-α. In arsenic trioxide and IFN-α treated group, the expression of proliferating cell nuclear antigen (PCNA) was reached a peak level at 0 hr and it was decreased from 12 hr to 48 hr after the treatment. PCNA is known to be associated with S phase and DNA replication of the cell cycle. Whereas, apoptotic index was reached a peak level at 48 hr after the treatment and it was nearly restored to the control level at 8 days. In conclusion, our results suggest that the combined treatment with arsenic trioxide and IFN-α inhibited the growth of LL2 tumor cells through the suppression of cell proliferation and the induction of apoptosis.
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Seo, Deug-Log,Yang, Je-Hoon,Won, Chung-Kil,Kim, Myeong-Ok,Lee, Jong-Hwan,Kwark, Soo-Dong,Koh, Phil-Ok The Korean Society of Veterinary Science 2005 大韓獸醫學會誌 Vol.45 No.1
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.
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