Sorafenib Enhances Radiation-Induced Apoptosis in Hepatocellular Carcinoma by Inhibiting STAT3
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China)
- School of Veterinary Medicine, National Taiwan University Hospital, Taipei, Taiwan (China)
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan (China)
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan (China)
Purpose: Hepatocellular carcinoma (HCC) is one of the most common and lethal human malignancies. Lack of efficient therapy for advanced HCC is a pressing problem worldwide. This study aimed to determine the efficacy and mechanism of combined sorafenib and radiation therapy treatment for HCC. Methods and Materials: HCC cell lines (PLC5, Huh-7, Sk-Hep1, and Hep3B) were treated with sorafenib, radiation, or both, and apoptosis and signal transduction were analyzed. Results: All 4 HCC cell lines showed resistance to radiation-induced apoptosis; however, this resistance could be reversed in the presence of sorafenib. Inhibition of phospho-STAT3 was found in cells treated with sorafenib or sorafenib plus radiation and subsequently reduced the expression levels of STAT3-related proteins, Mcl-1, cyclin D1, and survivin. Silencing STAT3 by RNA interference overcame apoptotic resistance to radiation in HCC cells, and the ectopic expression of STAT3 in HCC cells abolished the radiosensitizing effect of sorafenib. Moreover, sorafenib plus radiation significantly suppressed PLC5 xenograft tumor growth. Conclusions: These results indicate that sorafenib sensitizes resistant HCC cells to radiation-induced apoptosis via downregulating phosphorylation of STAT3 in vitro and in vivo.
- OSTI ID:
- 22224496
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 86; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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