Open Access

Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer

  • Authors:
    • Wei Wang
    • Linqing Liu
    • Yucheng Zhou
    • Qiang Ye
    • Xiuli Yang
    • Jinying Jiang
    • Ziqi Ye
    • Feng Gao
    • Xiaolu Tan
    • Guobing Zhang
    • Qingxia Fang
    • Zixue Xuan Xuan
  • View Affiliations

  • Published online on: June 12, 2019     https://doi.org/10.3892/ijo.2019.4824
  • Pages: 405-414
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer is an important cancer type worldwide, the anti‑angiogenic agent BC001 can target the vascular endothelial growth factor receptor 2 (VEGFR2), and significantly suppresses the growth of gastric cancer BGC823 cells in vitro and in vivo. However, numerous results indicated that antiangiogenic drugs could induce autophagy, and the inhibition of autophagy enhanced the anticancer effects of antiangiogenic agents. In the present study, hydroxychloroquine (HCQ), an inhibitor of autophagy, enhanced the antiproliferative and proapoptotic effects of BC001 in vitro. Furthermore, HCQ enhanced the antitumor effects of BC001 on BGC823 xenograft tumors in vivo. Of note, BC001 neither induced nor inhibited autophagy. RNA‑sequencing results revealed that HCQ regulated autophagy or lysosomal‑associated genes, such as tumor protein p53‑inducible nuclear protein 1, interleukin (IL)1B, tumor necrosis factor (TNF), Mediterranean fever, ubiquitin specific peptidase 36, IL6, neuraminidase (NEU)1, ATP‑binding cassette subfamily A member 1, proprotein convertase subtilisin/kexin type 9, myelin basic protein and NEU3. Importantly, HCQ was determined to affect multiple pathways, including ‘negative regulation of endothelial cell proliferation’, ‘blood vessel remodeling’, ‘cell surface receptor signaling pathways’ and ‘notch receptor processing’ associated with ‘signal transduction’, ‘cancers’ and ‘immune system’, through regulating C‑X‑C motif chemokine ligand 8, TNF, IL6, intercellular adhesion molecule 1 and FOS genes. In summary, HCQ was proposed to enhance the anticancer effects of BC001 in gastric cancer via complex mechanisms.
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August-2019
Volume 55 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Wang W, Liu L, Zhou Y, Ye Q, Yang X, Jiang J, Ye Z, Gao F, Tan X, Zhang G, Zhang G, et al: Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer. Int J Oncol 55: 405-414, 2019
APA
Wang, W., Liu, L., Zhou, Y., Ye, Q., Yang, X., Jiang, J. ... Xuan, Z. (2019). Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer. International Journal of Oncology, 55, 405-414. https://doi.org/10.3892/ijo.2019.4824
MLA
Wang, W., Liu, L., Zhou, Y., Ye, Q., Yang, X., Jiang, J., Ye, Z., Gao, F., Tan, X., Zhang, G., Fang, Q., Xuan, Z."Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer". International Journal of Oncology 55.2 (2019): 405-414.
Chicago
Wang, W., Liu, L., Zhou, Y., Ye, Q., Yang, X., Jiang, J., Ye, Z., Gao, F., Tan, X., Zhang, G., Fang, Q., Xuan, Z."Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer". International Journal of Oncology 55, no. 2 (2019): 405-414. https://doi.org/10.3892/ijo.2019.4824