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

Danyang Liu; Yang Hu; Ying Guo; Zhu Zhu; Bingzheng Lu; Xuelan Wang; Yijun Huang

doi:10.1371/journal.pone.0184578

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.

Authors

Danyang Liu¹, Yang Hu¹, Ying Guo², Zhu Zhu¹, Bingzheng Lu¹, Xuelan Wang¹, Yijun Huang¹

Affiliations

¹ Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
² State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, Guangzhou, China.

Abstract

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
Gemcitabine
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

Substances

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

Grants and funding

The authors received no specific funding for this work.