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Sinomenine hydrochloride enhancement of the inhibitory effects of anti-transferrin receptor antibody-dependent on the COX-2 pathway in human hepatoma cells

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Abstract

Transferrin receptor (TfR) has been used as a target for the antibody-based therapy of cancer due to its higher expression in tumors relative to normal tissues. Great potential has been shown by anti-TfR antibodies combined with chemotherapeutic drugs as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with sinomenine hydrochloride in vitro. Results suggested that anti-TfR mAb or sinomenine hydrochloride could induce apoptosis, inhibit proliferation, and affect the cell cycle. A synergistic effect was found in relation to tumor growth inhibition and the induction of apoptosis when anti-TfR mAb and sinomenine hydrochloride were used simultaneously. The expression of COX-2 and VEGF protein in HepG2 cells treated with anti-TfR mAb alone was increased in line with increasing dosage of the agent. In contrast, COX-2 expression was dramatically decreased in HepG2 cells treated with sinomenine hydrochloride alone. Furthermore, we demonstrated that the inhibitory effects of sinomenine hydrochloride and anti-TfR mAb administered in combination were more prominent than when the agents were administered singly. To sum up, these results showed that the combined use of sinomenine hydrochloride and anti-TfR mAb may exert synergistic inhibitory effects on human hepatoma HepG2 cells in a COX-2-dependent manner. This finding provides new insight into how tumor cells overcome the interference of iron intake to survive and forms the basis of a new therapeutic strategy involving the development of anti-TfR mAb combined with sinomenine hydrochloride for liver cancer.

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Acknowledgments

We thank Yue Zhang and Shuang Zou for their kind assistance in this study. This work was supported by funding from the National Natural Science Foundation of China (No. 81102531 to Xin Shen), the Important National Science and Technology Specific Projects (2009ZX09301-014 to Guanxin Shen), and the Young Foundation of Hubei Provincial Department of Education (Q20101804 to Yi Hong).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hongkong Road, Wuhan, 430030, People’s Republic of China

    Yi Hong, Juan Yang, Xin Shen, Huifen Zhu, Xiaoxu Sun, Xue Wen, Jing Bian, Heyu Hu, Lu Yuan, Ping Lei & Guanxin Shen

  2. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Yi Hong & Xin Shen

  3. Department of Dermatology, Affiliated Union Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China

    Juan Tao

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  1. Yi Hong
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  2. Juan Yang
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  3. Xin Shen
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  4. Huifen Zhu
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  5. Xiaoxu Sun
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  7. Jing Bian
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  8. Heyu Hu
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  9. Lu Yuan
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  10. Juan Tao
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  11. Ping Lei
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  12. Guanxin Shen
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Correspondence to Guanxin Shen.

Additional information

Yi Hong and Juan Yang contributed equally to the study and share first authorship.

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Hong, Y., Yang, J., Shen, X. et al. Sinomenine hydrochloride enhancement of the inhibitory effects of anti-transferrin receptor antibody-dependent on the COX-2 pathway in human hepatoma cells. Cancer Immunol Immunother 62, 447–454 (2013). https://doi.org/10.1007/s00262-012-1337-y

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  • DOI: https://doi.org/10.1007/s00262-012-1337-y

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