Jai-Jen Tsai1,2,3, Fei-Ting Hsu4,5,6, Po-Jung Pan2,7,8, Chia-Wen Chen9,10,11, Yu-Cheng Kuo12,13. 1. Division of Gastroenterology, Department of Medicine, National Yang-Ming University Hospital, I-Lan, Taiwan, R.O.C. 2. Cancer Medical Care Center, National Yang Ming University Hospital, I-Lan, Taiwan, R.O.C. 3. Department of Nursing, Cardinal Tien Junior College of Healthcare & Management, I-Lan, Taiwan, R.O.C. 4. Department of Radiology, School of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C. 5. Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C. 6. Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C. 7. Department of Physical Medicine and Rehabilitation, National Yang-Ming University Hospital, I-Lan, Taiwan, R.O.C. 8. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. 9. Department of Anesthesiology, School of Medicine, China Medical University, Taichung, Taiwan, R.O.C. 10. Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan, R.O.C. 11. Department of Anesthesiology, Asia University Hospital, Taichung, Taiwan, R.O.C. 12. Department of Radiation Oncology, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C. shapico22@gmail.com. 13. Department of Radiation Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND METHODS: HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight. RESULTS: Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways. CONCLUSION: Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo. Copyright
BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND METHODS: HCC SK-Hep1tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight. RESULTS: Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways. CONCLUSION:Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo. Copyright