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Article

Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor

  • Authors:
    • Shanshan Shi
    • Chenxing Yuan
    • Kaizan Zhuang
    • Guikai Liang
    • Zhangting Yao
    • Duoduo  Wang
    • Qinjie Weng
    • Ji Cao
    • Peihua Luo
    • Hong Zhu
    • Ling Ding
    • Shenglin Ma
  • View Affiliations / Copyright

    Affiliations: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China, Department of Pharmacy, Fenghua Hospital, Ningbo, Zhejiang 315040, P.R. China, Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310009, P.R. China
  • Pages: 3842-3847
    |
    Published online on: January 16, 2015
       https://doi.org/10.3892/mmr.2015.3217
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Abstract

Hypoxia is associated with resistance to chemotherapy in a number of human cancer types; particularly in hepatocellular carcinoma (HCC), which is a highly vascularized tumor. To develop a potential combination therapy strategy that is capable of overcoming the hypoxia‑induced insensitivity to chemotherapy, the HCC cell SMMC‑7721 was employed to investigate the hypoxia‑induced chemoresistance to etoposide. Increased levels of hypoxia‑inducible factor‑1α (HIF‑1α) and vascular endothelial growth factor (VEGF) were observed when SMMC‑7721 cells were exposed to hypoxia, and exposure of tumor cells to hypoxia impaired etoposide‑induced DNA damage, as indicated by the failure of upregulation of γHA2X. Etoposide‑induced apoptosis and cell cycle arrest of SMMC‑7721 was also impaired in hypoxia. However, co‑treatment with anti‑VEGF significantly restored etoposide‑induced cell apoptosis and cell cycle arrest, as indicated by the elimination of B‑cell lymphoma 2 (Bcl‑2), procaspase 3, cyclin B1 and Cdc2. Furthermore, anti‑VEGF eliminated phosphorylation of AKT, ERK and IκB‑α resulting from hypoxia, suggesting the involvement of VEGF in the activation of the survival pathways. In conclusion, the present study suggests a significant role of VEGF in the chemoresistance of etoposide in hypoxia. A rational chemotherapy should be developed based on a combination of etoposide and anti‑VEGF.
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Copy and paste a formatted citation
Spandidos Publications style
Shi S, Yuan C, Zhuang K, Liang G, Yao Z, Wang D, Weng Q, Cao J, Luo P, Zhu H, Zhu H, et al: Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor. Mol Med Rep 11: 3842-3847, 2015.
APA
Shi, S., Yuan, C., Zhuang, K., Liang, G., Yao, Z., Wang, D. ... Ma, S. (2015). Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor. Molecular Medicine Reports, 11, 3842-3847. https://doi.org/10.3892/mmr.2015.3217
MLA
Shi, S., Yuan, C., Zhuang, K., Liang, G., Yao, Z., Wang, D., Weng, Q., Cao, J., Luo, P., Zhu, H., Ding, L., Ma, S."Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor". Molecular Medicine Reports 11.5 (2015): 3842-3847.
Chicago
Shi, S., Yuan, C., Zhuang, K., Liang, G., Yao, Z., Wang, D., Weng, Q., Cao, J., Luo, P., Zhu, H., Ding, L., Ma, S."Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor". Molecular Medicine Reports 11, no. 5 (2015): 3842-3847. https://doi.org/10.3892/mmr.2015.3217
Copy and paste a formatted citation
x
Spandidos Publications style
Shi S, Yuan C, Zhuang K, Liang G, Yao Z, Wang D, Weng Q, Cao J, Luo P, Zhu H, Zhu H, et al: Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor. Mol Med Rep 11: 3842-3847, 2015.
APA
Shi, S., Yuan, C., Zhuang, K., Liang, G., Yao, Z., Wang, D. ... Ma, S. (2015). Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor. Molecular Medicine Reports, 11, 3842-3847. https://doi.org/10.3892/mmr.2015.3217
MLA
Shi, S., Yuan, C., Zhuang, K., Liang, G., Yao, Z., Wang, D., Weng, Q., Cao, J., Luo, P., Zhu, H., Ding, L., Ma, S."Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor". Molecular Medicine Reports 11.5 (2015): 3842-3847.
Chicago
Shi, S., Yuan, C., Zhuang, K., Liang, G., Yao, Z., Wang, D., Weng, Q., Cao, J., Luo, P., Zhu, H., Ding, L., Ma, S."Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor". Molecular Medicine Reports 11, no. 5 (2015): 3842-3847. https://doi.org/10.3892/mmr.2015.3217
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