Immunomodulatory action of excretory-secretory products of Angiostrongylus cantonensis in a mouse tumour model

Parasitol Res. 2020 Nov;119(11):3705-3718. doi: 10.1007/s00436-020-06872-4. Epub 2020 Sep 8.


Excretory-secretory products (ESPs) of parasitic helminths are well known to exert immunostimulation and immunomodulation in hosts. Immune regulation plays a key role in anti-tumour therapy. The present study explored the anti-tumour effect of ESPs released by Angiostrongylus cantonensis. In Hepa1-6 mouse tumour models, ESPs significantly reduced tumour growth. Tumour-bearing mice treated with ESPs had significantly higher CD3+, CD4+, and CD8+ T cell counts than those treated with Freund's adjuvant. In vitro, human hepatocarcinoma HepG2 cells, human lung cancer A549 cells, and normal human liver HL-7702 cells were co-incubated with ESPs for 24 h and 48 h. ESPs significantly accelerated HepG2 apoptosis but had no inhibitory effect on the proliferation of A549 and HL-7702 cells. Apoptotic HepG2 cells displayed condensed nuclei, apoptotic bodies, and swollen endoplasmic reticulum (ER). Expression of the endoplasmic reticulum stress (ERS)-related factors activating transcription factor 6 (ATF6) and C/EBP-homologous protein (CHOP) in HepG2 cells increased with increasing ESP concentration and treatment time. Calreticulin (CRT) is a key effector protein of ESPs, and recombinant calreticulin (rCRT) was produced in BL21 Escherichia coli (E. coli). In contrast to ESPs, rCRT markedly reduced the proliferation of HepG2 cells. The expression levels of ATF6 and CHOP in HepG2 cells treated with 30 μg/mL rCRT significantly increased at 48 h. Notably, these findings synergistically suggest that ESPs and rCRT are promising candidates for anti-tumour immunotherapy.

Keywords: Angiostrongylus cantonensis; Apoptosis; Calreticulin; Endoplasmic reticulum stress; Excretory-secretory products; Tumour.

MeSH terms

  • A549 Cells
  • Angiostrongylus cantonensis / genetics
  • Angiostrongylus cantonensis / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Calreticulin / genetics
  • Calreticulin / metabolism
  • Calreticulin / pharmacology
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Helminth Proteins / pharmacology
  • Hep G2 Cells
  • Humans
  • Immunologic Factors / metabolism
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology


  • Calreticulin
  • Helminth Proteins
  • Immunologic Factors
  • Recombinant Proteins