Apicidin-resistant HA22T hepatocellular carcinoma cells massively promote pro-survival capability via IGF-IR/PI3K/Akt signaling pathway activation

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• 作者：Hsi-Hsien Hsu (1) (2)
  Li-Hao Cheng (3)
  Tsung-Jung Ho (4)
  Wei-Wen Kuo (5)
  Yueh-Min Lin (6) (7)
  Ming-Cheng Chen (3) (8)
  Nien-Hung Lee (3)
  Fuu-Jen Tsai (9)
  Kun-Hsi Tsai (10) (11)
  Chih-Yang Huang (12) (3) (9)
  
• 关键词：Apicidin鈥A22T ; Hepatocellular carcinoma cells ; IGF ; IR路PI3K ; Akt
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：35
• 期：1
• 页码：303-313
• 全文大小：605 KB
• 作者单位：Hsi-Hsien Hsu (1) (2)
  Li-Hao Cheng (3)
  Tsung-Jung Ho (4)
  Wei-Wen Kuo (5)
  Yueh-Min Lin (6) (7)
  Ming-Cheng Chen (3) (8)
  Nien-Hung Lee (3)
  Fuu-Jen Tsai (9)
  Kun-Hsi Tsai (10) (11)
  Chih-Yang Huang (12) (3) (9)
  
  1. Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan
  2. Mackay Medicine, Nursing and Management College, Taipei, Taiwan
  3. Graduate Institute of Basic Medical Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 404, Taiwan, Republic of China
  4. Chinese Medicine Department, China Medical University Beigang Hospital, Beigang, Taiwan
  5. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
  6. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
  7. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
  8. Puli Branch, Taichung Veterans General Hospital, Nantou, Taiwan
  9. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
  10. Department of Emergency Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
  11. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
  12. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
  
• ISSN：1423-0380

文摘

Despite rapid advances in the diagnostic and surgical procedures, hepatocellular carcinoma (HCC) remains one of the most difficult human malignancies to treat. This may be due to the chemoresistant behaviors of HCC. It is believed that acquired resistance could be overcome and improve the overall survival of HCC patients by understanding the mechanisms of chemoresistance in HCC. A stable HA22T cancer line, which is chronically resistant to a histone deacetylase inhibitor, was established. After comparing the molecular mechanism of apicidin-R HA22T cells to parental ones by Western blotting, cell cycle-regulated proteins did not change in apicidin-R cells, but apicidin-R cells were more proliferative and had higher tumor growth (wound-healing assay and nude mice xenograft model). Moreover, apicidin-R cells displayed increased levels of p-IGF-IR, p-PI3K, p-Akt, Bcl-xL, and Bcl-2 but also significantly inhibited the tumor suppressor PTEN protein and apoptotic pathways when compared to the parental strain. Therefore, the highly proliferative effect of apicidin-R HA22T cells was blocked by Akt knockdown. For all these findings, we believe that novel strategies to attenuate IGF-IR/PI3K/Akt signaling could overcome chemoresistance toward the improvement of overall survival of HCC patients.