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2014-April Volume 31 Issue 4

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Article

PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus

  • Authors:
    • Yin Tong
    • Weiwei Zhu
    • Xianbo Huang
    • Liangshun You
    • Xiujun Han
    • Chunmei Yang
    • Wenbin Qian
  • View Affiliations / Copyright

    Affiliations: Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, P.R. China, Women's Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, P.R. China
  • Pages: 1581-1588
    |
    Published online on: February 11, 2014
       https://doi.org/10.3892/or.2014.3020
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Abstract

Recently, much progress has been achieved in the treatment of multiple myeloma (MM). However, the major challenge of chemotherapeutic drugs is acquired resistance. Oncolytic virotherapies offer promising alternatives; with the possibility of their integration with current therapeutic strategies. In the present study, we assessed the potential of ZD55-TRAIL (an oncolytic adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand) as an oncolytic agent for MM. Our results clearly indicated that ZD55 armed with TRAIL was more cytotoxic to drug-sensitive as well as drug-resistant MM cell lines, than the virus alone. Furthermore, it was also observed that ZD55-TRAIL induced apoptosis through the activation of the caspase pathway. In particular, ZD55-TRAIL significantly inhibited insulin-like growth factor-1 receptor (IGF-1R) and NFκB. However, IGF did not abrogate ZD55‑TRAIL-induced cell death. Combination of ZD55-TRAIL with the PI3K inhibitor LY294002 in RPMI‑8226 cells inhibited the virus‑mediated activation of mTOR and AKT, thus, promoting cell death. Combined treatment of ZD55-TRAIL and MG132 (a proteasome inhibitor) robustly increased the expression of death receptor 5 (DR5), which enhanced the apoptosis response without significant toxicity to normal liver cells. Collectively, our results suggest that combined treatment of TRAIL-armed oncolytic adenovirus and a PI3K inhibitor or a proteosome inhibitor may serve as a promising therapy for MM.
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Copy and paste a formatted citation
Spandidos Publications style
Tong Y, Zhu W, Huang X, You L, Han X, Yang C and Qian W: PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus. Oncol Rep 31: 1581-1588, 2014.
APA
Tong, Y., Zhu, W., Huang, X., You, L., Han, X., Yang, C., & Qian, W. (2014). PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus. Oncology Reports, 31, 1581-1588. https://doi.org/10.3892/or.2014.3020
MLA
Tong, Y., Zhu, W., Huang, X., You, L., Han, X., Yang, C., Qian, W."PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus". Oncology Reports 31.4 (2014): 1581-1588.
Chicago
Tong, Y., Zhu, W., Huang, X., You, L., Han, X., Yang, C., Qian, W."PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus". Oncology Reports 31, no. 4 (2014): 1581-1588. https://doi.org/10.3892/or.2014.3020
Copy and paste a formatted citation
x
Spandidos Publications style
Tong Y, Zhu W, Huang X, You L, Han X, Yang C and Qian W: PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus. Oncol Rep 31: 1581-1588, 2014.
APA
Tong, Y., Zhu, W., Huang, X., You, L., Han, X., Yang, C., & Qian, W. (2014). PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus. Oncology Reports, 31, 1581-1588. https://doi.org/10.3892/or.2014.3020
MLA
Tong, Y., Zhu, W., Huang, X., You, L., Han, X., Yang, C., Qian, W."PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus". Oncology Reports 31.4 (2014): 1581-1588.
Chicago
Tong, Y., Zhu, W., Huang, X., You, L., Han, X., Yang, C., Qian, W."PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus". Oncology Reports 31, no. 4 (2014): 1581-1588. https://doi.org/10.3892/or.2014.3020
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