Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
August-2019 Volume 55 Issue 2

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2019 Volume 55 Issue 2

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article 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 / Copyright

    Affiliations: Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Geriatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China, Department of General Surgery, Key Laboratory of Gastroenterology of Zhejiang, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Buchang (Beijing) Pharmaceutical R&D Co., Ltd., Beijing 100176, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 405-414
    |
    Published online on: June 12, 2019
       https://doi.org/10.3892/ijo.2019.4824
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Sharma MR, Joshi SS, Karrison TG, Allen K, Suh G, Marsh R, Kozloff MF, Polite BN, Catenacci DVT and Kindler HLA: A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies. Cancer. 125:1629–1636. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Viallard C and Larrivée B: Tumor angiogenesis and vascular normalization: Alternative therapeutic targets. Angiogenesis. 20:409–426. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, et al: A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 370:699–708. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Javle M, Smyth EC and Chau I: Ramucirumab: Successfully targeting angiogenesis in gastric cancer. Clin Cancer Res. 20:5875–5881. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Xuan ZX, Li LN, Zhang Q, Xu CW, Yang DX, Yuan Y, An YH, Wang SS, Li XW and Yuan SJ: Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth. Int J Oncol. 45:2411–2420. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Han K, Jin J, Maia M, Lowe J, Sersch MA and Allison DE: Lower exposure and faster clearance of bevacizumab in gastric cancer and the impact of patient variables: Analysis of individual data from AVAGAST phase III trial. AAPS J. 16:105610632014. View Article : Google Scholar : PubMed/NCBI

8 

Hu Y-L, Jahangiri A, De Lay M and Aghi MK: Hypoxia-induced tumor cell autophagy mediates resistance to anti-angiogenic therapy. Autophagy. 8:979–981. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Levy JMM, Towers CG and Thorburn A: Targeting autophagy in cancer. Nat Rev Cancer. 17:528–542. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Mokarram P, Albokashy M, Zarghooni M, Moosavi MA, Sepehri Z, Chen QM, Hudecki A, Sargazi A, Alizadeh J, Moghadam AR, et al: New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets. Autophagy. 13:781–819. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Cook KL, Warri A, Soto- Pantoja DR, Clarke PA, Cruz MI, Zwart A and Clarke R: Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res. 20:3222–3232. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, Mikkelson T, Wang D, Chang YC, Hu J, et al: A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 10:1359–1368. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Selvakumaran M, Amaravadi RK, Vasilevskaya IA and O'Dwyer PJ: Autophagy inhibition sensitizes colon cancer cells to antiangiogenic and cytotoxic therapy. Clin Cancer Res. 19:2995–3007. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Chiu CH, Lei KF, Yeh WL, Chen P, Chan YS, Hsu KY and Chen AC: Comparison between xCELLigence biosensor technology and conventional cell culture system for real-time monitoring human tenocytes proliferation and drugs cytotoxicity screening. J Orthop Surg Res. 12:1492017. View Article : Google Scholar : PubMed/NCBI

15 

Wang Y, Zhang J, Huang Z-H, Huang X-H, Zheng W-B, Yin X-F, Li Y-L, Li B and He Q-Y: Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2- p62- keap1 feedback loop. Cell Death Dis. 8:e28762017. View Article : Google Scholar

16 

Gump JM and Thorburn A: Sorting cells for basal and induced autophagic flux by quantitative ratiometric flow cytometry. Autophagy. 10:1327–1334. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Alirezaei M, Flynn CT, Wood MR, Harkins S and Whitton JL: Coxsackievirus can exploit LC3 in both autophagy- dependent and - independent manners in vivo. Autophagy. 11:1389–1407. 2015. View Article : Google Scholar :

18 

Dong J-K, Lei H-M, Liang Q, Tang Y-B, Zhou Y, Wang Y, Zhang S, Li W-B, Tong Y, Zhuang G, et al: Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase. Theranostics. 8:1808–1823. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Han J, Chen M, Wang Y, Gong B, Zhuang T, Liang L and Qiao H: Identification of biomarkers based on differentially expressed genes in papillary thyroid carcinoma. Sci Rep. 8:99122018. View Article : Google Scholar : PubMed/NCBI

20 

Pirola L, Ciesielski O and Balcerczyk A: The methylation status of the epigenome: Its emerging role in the regulation of tumor angiogenesis and tumor growth, and potential for drug targeting. Cancers (Basel). 10:2682018. View Article : Google Scholar

21 

Mulcahy Levy JM, Zahedi S, Griesinger AM, Morin A, Davies KD, Aisner DL, Kleinschmidt-DeMasters BK, Fitzwalter BE, Goodall ML, Thorburn J, et al: Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors. eLife. 6:e196712017. View Article : Google Scholar : PubMed/NCBI

22 

Zhao Z, Xia G, Li N, Su R, Chen X and Zhong L: Autophagy inhibition promotes bevacizumab- induced apoptosis and proliferation inhibition in colorectal cancer cells. J Cancer. 9:3407–3416. 2018. View Article : Google Scholar :

23 

Maes H, Kuchnio A, Carmeliet P and Agostinis P: Chloroquine anticancer activity is mediated by autophagy-independent effects on the tumor vasculature. Mol Cell Oncol. 3:e9700972015. View Article : Google Scholar

24 

Chen D, Xie J, Fiskesund R, Dong W, Liang X, Lv J, Jin X, Liu J, Mo S, Zhang T, et al: Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun. 9:8732018. View Article : Google Scholar : PubMed/NCBI

25 

Huang H, Wang Y, Cao Y, Wu B, Li Y, Fan L, Tan Z, Jiang Y, Tang J, Hu J, et al: Interleukin- 6, tumor necrosis factor- alpha and receptor activator of nuclear factor kappa ligand are elevated in hypertrophic gastric mucosa of pachydermoperiostosis. Sci Rep. 7:96862017. View Article : Google Scholar

26 

Yin S, Xia C, Wang Y, Wan D, Rao J, Tang X, Wei J, Wang X, Li M, Zhang Z, et al: Dual receptor recognizing liposomes containing paclitaxel and hydroxychloroquine for primary and metastatic melanoma treatment via autophagy-dependent and independent pathways. J Control Release. 288:148–160. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Figenschau SL, Knutsen E, Urbarova I, Fenton C, Elston B, Perander M, Mortensen ES and Fenton KA: ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes. Sci Rep. 8:117202018. View Article : Google Scholar : PubMed/NCBI

28 

van IJzendoorn DGP, Forghany Z, Liebelt F, Vertegaal AC, Jochemsen AG, Bovée JVMG, Szuhai K and Baker DA: Functional analyses of a human vascular tumor FOS variant identify a novel degradation mechanism and a link to tumorigenesis. J Biol Chem. 292:21282–21290. 2017. View Article : Google Scholar : PubMed/NCBI

29 

National Research Council: Guide for the Care and Use of Laboratory Animals. 8th edition. The National Academies Press; Washington, DC: 2011

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team