Mycoplasma-associated multidrug resistance of hepatocarcinoma cells requires the interaction of P37 and Annexin A2

PLoS One. 2017 Oct 4;12(10):e0184578. doi: 10.1371/journal.pone.0184578. eCollection 2017.


Mycoplasma infection has been reported to be associated with cancer migration, invasion, epithelial-mesenchymal transition as well as the resistance to nucleoside analogues chemotherapeutic drugs. In this study, we found that the sensitivity of hepatocarcinoma cells to Cisplatin, Gemcitabine and Mitoxantrone was increased by mycoplasma elimination. Similar to the effect of anti-mycoplasma agent, interrupting the interaction between Mycoplasma hyorhinis membrane protein P37 and Annexin A2 of host cells using the N-terminal of ANXA2 polypeptide enhanced the sensitivity of HCC97L cells to Gemcitabine and Mitoxantrone. Meanwhile, we did not observe any changes in expression or distribution of multidrug resistance associated transporters, ATP-Binding Cassette protein B1, C1 and G2, on the removal of mycoplasma. These results suggest that mycoplasma induces a resistance to multiple drugs in hepatocarcinoma cells which required the interaction of P37 and Annexin A2. The pathway downstream this interaction needs to be explored.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Annexin A2 / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Azithromycin / pharmacology
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / microbiology
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Fluoroquinolones / pharmacology
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / microbiology
  • Liver Neoplasms / pathology*
  • Mitoxantrone / pharmacology
  • Moxifloxacin
  • Mycoplasma hyorhinis / drug effects
  • Mycoplasma hyorhinis / genetics
  • Mycoplasma hyorhinis / isolation & purification
  • Mycoplasma hyorhinis / physiology*
  • Protein Binding
  • Real-Time Polymerase Chain Reaction


  • Adaptor Proteins, Signal Transducing
  • Annexin A2
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Fluoroquinolones
  • p37 protein, human
  • Deoxycytidine
  • Azithromycin
  • gemcitabine
  • Mitoxantrone
  • Moxifloxacin

Grant support

The authors received no specific funding for this work.