SC144 showed its function through both exhibiting potent cytotoxicity, by itself or synergism with other compounds, against a panel of drug-sensitive and drug-resistant cancer cell lines, and targeting to gp130.
Drug resistance is caused by various cellular mechanism. One of the most important factors is the expression of a group of genes encoding ATP-dependent transporters of particular importance in drug resistance. SC144 showed its function through both exhibiting potent cytotoxicity, by itself or synergism with other compounds, against a panel of drug-sensitive and drug-resistant cancer cell lines, and targeting to gp130. Treatment with SC144 induced p-gp130-S782 in a time (2μM, 5min-6h)- and dose (0.5-2μM)-dependent manner in both OVCAR-8 and Caov-3 cells, suggesting the downregulation of cell surface expression of gp130. Consistent with the induced phosphorylation, the suppression on Stat3 signaling pathway, a downstream signaling cascade of gp130, and its target gene expression, including decrease of constitutive phosphorylation of Stat3, Survivin, MMP-7, D1, Bcl-XL, Bcl-2 and Ape1/Ref-1, can be observed after treatment with SC144 both in vitro and in vivo. For Gp130 is part of the receptor signaling complexes for at least 8 cytokines, suppression of gp130 by SC144 can inhibit downstream signaling induced by gp130 cytokines, including p-Stat3, p-Stat1 and p-Akt induced by LIF or Il-6. Daily intraperitoneal injection of SC144 at 10 mg/kg 5 days on and 2 days off for 58 days significantly inhibited OVCAR-8 tumor growth in mice[1]. Treatment with SC144 alone can cause growth inhibition of HT29 colon cancer cells with IC50 value of 0.9μM. Combined treatment with SC144 significantly enhanced the cytotoxicity of oxaliplatin in oxaliplatin-resistant HTOXAR3 cells. Co-treatment of SC144 with oxaliplatin in HT29 cells caused cell cycle arrest halting at S-phase[2].
SC144 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
HCT116 cells
Cytotoxicity assay
72 h
Cytotoxicity against human HCT116 cells expressing p53 gene after 72 hrs by MTT assay, IC50=0.6 μM
17085054
HCT116 cells
Cytotoxicity assay
72 h
Cytotoxicity against p53 deficient human HCT116 cells after 72 hrs by MTT assay, IC50=0.9 μM
17085054
HT29 cells
Cytotoxicity assay
72 h
Cytotoxicity against human HT29 cells after 72 hrs by MTT assay, IC50=0.9 μM
17085054
LNCap cells
Cytotoxicity assay
72 h
Cytotoxicity against human LNCap cells after 72 hrs by MTT assay, IC50=0.4 μM
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