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Effects of STAT3 Gene Silencing and Rapamycin on Apoptosis in Hepatocarcinoma Cells

By Yi Zhang, Jun-Wei Zhang, Guo-Yue Lv, Shu-Li Xie and Guang-Yi Wang


The PI3K/Akt/mTOR and JAK/STAT3 signaling pathways are important for regulating apoptosis, and are frequently activated in cancers. In this study, we targeted STAT3 and mTOR in human hepatocellular carcinoma Bel-7402 cells and examined the subsequent alterations in cellular apoptosis. The expression of STAT3 was silenced with small interfering RNA (siRNA)-expressing plasmid. The activity of mTOR was inhibited using rapamycin. Following treatment, Annexin V/propidium iodide staining followed by flow cytometry and Hoechst33258 immunofluorescence staining was used to examine cellular apoptosis. JC-1 staining was used to monitor depolarization of mitochondrial membrane (ΔΨm). Furthermore, the expression of activated caspase 3 protein was analyzed by Western blotting. Compared to non-treated or control siRNA-transfected cells, significantly higher levels of apoptosis were detected in siSTAT3-transfected or rapamycin-treated cells (P < 0.05), which was further enhanced in cells targeted for both molecules (P < 0.05). The pro-apoptotic effects were accompanied with concomitant depolarization of mitochondrial membrane and up-regulation of activated caspase 3. Combined treatments using rapamycin and STAT3 gene silencing significantly increases apoptosis in Bel-7402 cells, displaying more dramatic effect than any single treatment. This study provides evidence for targeting multiple molecules in cancer therapy

Topics: Research Paper
Publisher: Ivyspring International Publisher
OAI identifier: oai:pubmedcentral.nih.gov:3298013
Provided by: PubMed Central
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    1. (2009). Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. Endocr Relat Cancer.
    2. Effects of rapamycin on cell proliferation and phosphorylation of mTOR and
    3. Evaluation of potential Stat3-regulated genes in human breast cancer.
    4. Functional Identification of Optimized RNAi Triggers Using a Massively Parallel Sensor Assay. Molecular Cell.
    5. (2007). Genetic progression and the waiting time to cancer. PLoS Comput Biol.
    6. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases.
    7. Hepatocellular carcinom: epidemiology and molecular cacinogenesis.
    8. Inflammation and cancer:
    9. (2006). Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription3. Clin Cancer Res.
    10. Inhibition of mammalian target of rapamycin as a therapeutic strategy in the management of bladder cancer.
    11. Interleukin-27 directly induces differentiation in hematopoietic stem cells.
    12. (1997). Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. Cancer Res.
    13. Linking oncogenic pathways with therapeutic opportunities.
    14. Molecular and functional genetics of hepatocellular carcinoma.
    15. mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther.
    16. mTOR signaling: implications for cancer and anticancer therapy.
    17. Rapamycin and CCI-779 inhibit the mammalian target of rapamycin signalling in hepatocellular carcinoma. Liver Int.
    18. Rheb-mTOR signaling pathway involved in tumor formation. Tanpakushitsu Kakusan Koso.
    19. Roles of activated Src and Stat3 signaling in melanoma tumor cell growth.
    20. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Current Biology.
    21. Somatic evolution of cancer cells.
    22. STAT3 as a target for inducing apoptosis in solid and hematological tumors. Cell Res.
    23. Targeting mTOR in renal cell carcinoma.
    24. The mTOR pathway and its role in human genetic diseases. Mutat Res.
    25. (2010). The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochem Biophys Res Commun.
    26. Updated treatment approach to hepatocellular carcinoma.

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