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Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells

  • Authors:
    • Chao Wang
    • Lingfei Wang
    • Beibei Liang
    • Bo Zhou
    • Yu Sun
    • Yanchun Meng
    • Jian Dong
    • Lin Chen
    • Bohua Li
  • View Affiliations / Copyright

    Affiliations: Department of Cell Biology, Navy Medical University (The Second Military Medical University), Shanghai 200433, P.R. China, Department of Oncology, The 903rd Hospital of The Chinese People's Liberation Army, Hangzhou, Zhejiang 310013, P.R. China, School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P.R. China, Basic Medicine Faculty, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P.R. China, Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China, Department of Vascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of Colorectal Surgery, Affiliated to The Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China, Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 400
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    Published online on: March 18, 2021
       https://doi.org/10.3892/ol.2021.12661
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Abstract

Trastuzumab resistance is a severe problem in the treatment of ErbB2‑amplified cancer. Although trastuzumab plus pertuzumab is able to partly overcome trastuzumab resistance in ErbB2‑overexpressing cancer, its antitumor efficacy remains limited. The present study investigated the antitumor activity of the combination of trastuzumab with H2‑18, which is an antibody targetinsg ErbB2 domain I. Cell proliferation and inhibition experiments indicated that H2‑18 and trastuzumab synergistically inhibited the proliferation of both the trastuzumab‑sensitive gastric cancer cell line, NCI‑N87 and the trastuzumab‑resistant gastric cancer cell line, NCI‑N87‑TraRT. Furthermore, H2‑18 plus trastuzumab inhibited the growth of NCI‑N87‑TraRT cells more effectively than trastuzumab plus pertuzumab, both in vitro and in vivo. Compared with trastuzumab plus pertuzumab, H2‑18 plus trastuzumab had a potent ability to inhibit NCI‑N87‑TraRT cells to form colonies. Notably, H2‑18 plus trastuzumab was more effective in inducing cell death than trastuzumab plus pertuzumab. The in vivo studies demonstrated that H2‑18 plus trastuzumab effectively inhibited the growth of both NCI‑N87 and NCI‑N87‑TraRT xenograft tumors. Further experiments revealed that in NCI‑N87‑TraRT cells, H2‑18 plus trastuzumab was comparable to trastuzumab plus pertuzumab in the inhibition of phosphorylated (p‑)HER3, p‑AKT and p‑ERK. However, compared with trastuzumab plus pertuzumab, H2‑18 plus trastuzumab effectively activated ROS production and the phosphorylation of JNK and c‑jun in NCI‑N87‑TraRT cells. Therefore, the superior antitumor efficacy of H2‑18 plus trastuzumab over trastuzumab plus pertuzumab may be mainly attributable to the potent cell death‑inducing activity. In addition, the in vitro and in vivo antitumor effect of the combination of H2‑18, trastuzumab and pertuzumab were further investigated. The results revealed that H2‑18 plus trastuzumab plus pertuzumab exhibited a maximal antitumor effect among all the anti‑ErbB2 monoclonal antibody combinations tested. In summary, H2‑18 plus trastuzumab may have potential as an effective strategy to overcome the resistance to trastuzumab in ErbB2‑amplified gastric cancer cell lines.
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Copy and paste a formatted citation
Spandidos Publications style
Wang C, Wang L, Liang B, Zhou B, Sun Y, Meng Y, Dong J, Chen L and Li B: Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells. Oncol Lett 21: 400, 2021.
APA
Wang, C., Wang, L., Liang, B., Zhou, B., Sun, Y., Meng, Y. ... Li, B. (2021). Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells. Oncology Letters, 21, 400. https://doi.org/10.3892/ol.2021.12661
MLA
Wang, C., Wang, L., Liang, B., Zhou, B., Sun, Y., Meng, Y., Dong, J., Chen, L., Li, B."Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells". Oncology Letters 21.5 (2021): 400.
Chicago
Wang, C., Wang, L., Liang, B., Zhou, B., Sun, Y., Meng, Y., Dong, J., Chen, L., Li, B."Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells". Oncology Letters 21, no. 5 (2021): 400. https://doi.org/10.3892/ol.2021.12661
Copy and paste a formatted citation
x
Spandidos Publications style
Wang C, Wang L, Liang B, Zhou B, Sun Y, Meng Y, Dong J, Chen L and Li B: Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells. Oncol Lett 21: 400, 2021.
APA
Wang, C., Wang, L., Liang, B., Zhou, B., Sun, Y., Meng, Y. ... Li, B. (2021). Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells. Oncology Letters, 21, 400. https://doi.org/10.3892/ol.2021.12661
MLA
Wang, C., Wang, L., Liang, B., Zhou, B., Sun, Y., Meng, Y., Dong, J., Chen, L., Li, B."Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells". Oncology Letters 21.5 (2021): 400.
Chicago
Wang, C., Wang, L., Liang, B., Zhou, B., Sun, Y., Meng, Y., Dong, J., Chen, L., Li, B."Synergistic antitumor effect of the anti‑ErbB2 antibodies trastuzumab and H2‑18 on trastuzumab‑resistant gastric cancer cells". Oncology Letters 21, no. 5 (2021): 400. https://doi.org/10.3892/ol.2021.12661
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