Open Access

Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy

  • Authors:
    • Dian‑Xing Liu
    • Peng‑Peng Li
    • Jia‑Pei Guo
    • Lei‑Lei Li
    • Bin Guo
    • Hong‑Bin Jiao
    • Jing‑Hua Wu
    • Jun‑Mao Chen
  • View Affiliations

  • Published online on: October 16, 2018     https://doi.org/10.3892/ol.2018.9584
  • Pages: 323-331
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer, which is the second leading cause of tumor‑associated mortality, is of great concern worldwide due to its resistance to chemotherapeutic drugs. Transcatheter arterial chemoembolization (TACE) has previously been used as a treatment for unresectable liver tumors in China; however, the response to TACE treatment differs between patients. It has been reported that hepatitis B virus (HBV)‑as sociated tumors are less sensitive to TACE treatment compared with non‑HBV‑associated liver cancer. Previous studies have demonstrated that exosomes serve a crucial role in hepatic carcinoma chemoresistance. We therefore hypothesized that HBV may modulate chemosensitivity via exosomes. The aim of the present study was to investigate how exosomes affect chemoresistance by assessing their role in chaperone‑mediated autophagy (CMA)‑dependent chemoresistance in HBV‑associated liver cancer. Iconography data from HBV‑positive and HBV‑negative patients with hepatic carcinoma receiving TACE treatment were assessed, and it was revealed that the tumor volume was decreased in the patients with non‑HBV‑associated liver cancer compared with that in the patients with HBV‑associated tumors following TACE therapy. Furthermore, it was revealed that exosomes from HBV‑infected liver cancer cells were able to downregulate cell apoptosis when treated with oxaliplatin compared with exosomes from normal HepG2 cells. Furthermore, the results demonstrated that HBV‑associated exosomes modulate cell death via activating the CMA pathway, and its key molecule, lysosome‑associated membrane protein (Lamp2a), was also upregulated. Lamp2a‑knockdown was also found to reverse anti‑apoptotic effects in liver cancer. Taken together, the results of the present study suggest that chemoresistance in patients with HBV‑associated hepatic tumors may be mediated by exosomes, and thus may provide a basis for the development of novel treatment strategies for chemoresistant liver cancer.
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January-2019
Volume 17 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liu DX, Li PP, Guo JP, Li LL, Guo B, Jiao HB, Wu JH and Chen JM: Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy. Oncol Lett 17: 323-331, 2019.
APA
Liu, D., Li, P., Guo, J., Li, L., Guo, B., Jiao, H. ... Chen, J. (2019). Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy. Oncology Letters, 17, 323-331. https://doi.org/10.3892/ol.2018.9584
MLA
Liu, D., Li, P., Guo, J., Li, L., Guo, B., Jiao, H., Wu, J., Chen, J."Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy". Oncology Letters 17.1 (2019): 323-331.
Chicago
Liu, D., Li, P., Guo, J., Li, L., Guo, B., Jiao, H., Wu, J., Chen, J."Exosomes derived from HBV‑associated liver cancer promote chemoresistance by upregulating chaperone‑mediated autophagy". Oncology Letters 17, no. 1 (2019): 323-331. https://doi.org/10.3892/ol.2018.9584