Background
Constitutive activation of STAT3 promotes oncogenesis and growth of oral squamous cell carcinoma (OSCC). We investigated the mechanism of action of suppressor of cytokine signaling 1 ...(SOCS1), an endogenous inhibitor of JAK, as gene therapy for OSCC.
Methods
Antitumor effect of SOCS1 was compared to JAK inhibitor I by cell proliferation assay, cell cycle analysis, and apoptosis analysis in vitro. In addition, antitumor effect was evaluated using xenograft mouse models in vivo.
Results
JAK inhibitor I inhibited the proliferation of KOSC2 cl3‐43 or T3M‐1 clone2 OSCC cell lines in vitro. While JAK inhibitor I arrested both cell lines at the G2/M phase, induction of apoptosis was observed in T3M‐1 clone2 cells, but not KOSC2‐cl3‐43 cells. An adenoviral vector expressing SOCS1 (AdSOCS1) significantly decreased the proliferation of both OSCC cell lines and induced G2/M phase cell cycle arrest and apoptosis, suggesting that induction of apoptosis of KOSC2 cl3‐43 cells by AdSOCS1 is regulated by the JAK/STAT independent pathway. Overexpression of SOCS1 inhibited activation of the JAK/STAT and p44/42 MAPK pathways, while JAK inhibitor I inhibited activation of the JAK/STAT pathway only. Consistently, expression of Mcl‐1 was decreased by overexpression of SOCS1, but not JAK inhibitor I. Additionally, KOSC2 cl3‐43 or T3M‐1 clone2 OSCC cells were subcutaneously implanted in the flanks of two xenograft mouse models. As compared to a control adenovirus vector (AdLacZ), intratumor injection of AdSOCS1 significantly decreased the tumor volume and induced apoptosis in vivo.
Conclusion
SOCS1 gene therapy may be a beneficial approach for the treatment of OSCC.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To clarify the relationship between the food availability for pollock larvae and the hydrographic conditions in Funka Bay (Hokkaido, Japan), horizontal distributions of water temperature, salinity ...and Oithona nauplii (main food for larval pollock) were investigated in winter from 2001 to 2003 in and near the bay. In January 2001 and 2003, the Oyashio coastal cold-water mass and the Tsugaru warm-water mass were co-distributed in the bay and its mouth region, but in January 2002, the Oyashio coastal cold-water mass has already exchanged with the Tsugaru warm-water mass. The median abundances of Oithona nauplii in January of each year were not different significantly. In January 2003, the density of female O. similis (main producer of Oithona nauplii) was higher in the Oyashio coastal cold-water mass than in the Tsugaru warm-water mass, while the densities of Oithona N1 in the Oyashio coastal cold-water mass and the Tsugaru warm-water mass were almost identical. These data indicate that the high activity of the individual reproduction is occurred in the Tsugaru warm water. From the results, it is considered that the warm-water temperature and the reproduction of O. similis in the Tsugaru warm-water mass in winter in Funka Bay support the larval feeding success.
To clarify the relationship between the food availability for pollock larvae and the hydrographic conditions in Funka Bay, horizontal distributions of water temperature, salinity and Oithona nauplii ...(main food for larval pollock) were investigated in winter from 2001 to 2003 in and near the bay. In January 2001 and 2003, the Oyashio coastal cold-water mass and the Tsugaru warm-water mass were co-distributed in the bay and its mouth region, but in January 2002, the Oyashio coastal cold-water mass has already exchanged with the Tsugaru warm-water mass. The median abundances of Oithona nauplii in January of each year were not different significantly. In January 2003, the density of female O. similis (main producer of Oithona nauplii) was higher in the Oyashio coastal cold-water mass than in the Tsugaru warm-water mass, while the densities of Oithona N1 in the Oyashio coastal cold-water mass and the Tsugaru marm-water mass were almost identical. These data indicate that the high activity of the individual reproduction is occurred in the Tsugaru warm water. From the results, it is considered that the warm-water temperature and the reproduction of O. similis in the Tsugaru warm-water mass in winter in Funka Bay support the larval feeding success.
