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- W2332823349 abstract "Hepatocellular carcinoma is a major worldwide public health problem, and the third most frequent cause of cancer deaths after lung and stomach cancers. Hepatocellular carcinoma is a highly malignant tumor type with average survival rates that are currently less than 1 year following diagnosis. The etiology of hepatocellular carcinoma is still not well understood but involves a multi‐step process of signaling protein dysregulation, which includes STAT3. The constitutive activation of STAT3 is frequently detected in clinical incidences of hepatocellular carcinoma and in more than 50% of human hepatocellular carcinoma cell lines but not in normal human hepatocytes. Constitutive STAT3 signaling contributes to hepatocellular carcinoma progression by promoting angiogenesis, survival, metastasis, and growth of hepatocellular carcinoma cells. Recent evidence suggests that the blockade of aberrant STAT3 signal pathway can be exploited as a therapeutic strategy for hepatocellular carcinoma. We have developed a novel small molecular STAT3 inhibitor LLL12 based on computer‐aided rational design, which inhibits STAT3 activity by binding to its Src homology 2 (SH2) domain. LLL12 can inhibit STAT3 tyrosine 705 phosphroylation, STAT3 DNA binding activitivies. and prevent STAT translocation into the nucleus, thus decrease the transcription of target genes. And LLL12 also can inhibit IL‐6 induced STAT3 phorsphorylation in Hep3B hepatocellular carcinoma cell. Our previous data show it can inhibit breast cancer (MDA‐MB231 cells), brain tumor (U87 cells), and pancreatic cancer (PANC‐1 cells) in vitro and in vivo. In this study, we report that LLL12 can selectively inhibit proliferation and induce apoptosis in SNU398, SNU387, Hep3B, and SNU449 hepatocellular carcinoma cells in vitro. Furthermore, the LLL12 can significantly inhibit tumor growth of SNU398 hepatocellular carcinoma cell line xenograft in nude mice at the dose of 5mg/kg. Collectively, our results show LLL12 could be used as a targeted drug candidate to target STAT3 for chemoprevention or treatment of Hepatocellular carcinoma in human. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B95." @default.
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- W2332823349 date "2010-01-07" @default.
- W2332823349 modified "2023-09-25" @default.
- W2332823349 title "Abstract B95: A novel small molecule, LLL12 inhibits STAT3 phosphorylation and activities and exhibits potent growth suppressive activity in human hepatocellular carcinoma cells" @default.
- W2332823349 doi "https://doi.org/10.1158/1940-6207.prev-09-b95" @default.
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