Cao Qi, Lu Xin, Feng You-Ji
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Cell Res. 2006 Jul;16(7):671-7. doi: 10.1038/sj.cr.7310078.
Although glycogen synthase kinase-3 (GSK-3) might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3beta may contribute to NF-kappaB activation in cancer cells leading to increased cancer cell proliferation and survival. Here we report that GSK-3beta activity was involved in the proliferation of human ovarian cancer cell both in vitro and in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed proliferation of the ovarian cancer cells. Overexpressing constitutively active form of GSK-3beta induced entry into the S phase, increased cyclin D1 expression and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3 inhibition prevented the formation of the tumor in nude mice generated by the inoculation of human ovarian cancer cells. Our findings thus suggest that GSK-3beta activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer.
尽管糖原合酶激酶-3（GSK-3）可能作为一种肿瘤抑制因子，因为预计其抑制作用会模拟Wnt信号通路的激活，但GSK-3β可能在癌细胞中促进核因子κB的激活，从而导致癌细胞增殖和存活增加。在此我们报告，GSK-3β活性在体外和体内均参与人卵巢癌细胞的增殖。用药物抑制剂抑制GSK-3活性可抑制卵巢癌细胞的增殖。过表达组成型活性形式的GSK-3β可诱导细胞进入S期，增加细胞周期蛋白D1的表达并促进卵巢癌细胞的增殖。此外，抑制GSK-3可阻止接种人卵巢癌细胞的裸鼠体内肿瘤的形成。因此，我们的研究结果表明，GSK-3β活性对卵巢癌细胞的增殖很重要，这意味着该激酶是卵巢癌潜在的治疗靶点。
