Cervical Cancer Correlates with the Differential Expression of Nicotinic Acetylcholine Receptors and Reveals Therapeutic Targets

Mar Drugs. 2019 Apr 28;17(5):256. doi: 10.3390/md17050256.

Abstract

Nicotinic acetylcholine receptors (nAChRs) are associated with various cancers, but the relation between nAChRs and cervical cancer remains unclear. Therefore, this study investigated the differential expression of nAChR subunits in human cervical cancer cell lines (SiHa, HeLa, and CaSki) and in normal ectocervical cell lines (Ect1/E6E7) at mRNA and protein levels. Two specific nAChR subtype blockers, αO-conotoxin GeXIVA and α-conotoxin TxID, were then selected to treat different human cervical cancer cell lines with specific nAChR subtype overexpression. The results showed that α3, α9, α10, and β4 nAChR subunits were overexpressed in SiHa cells compared with that in normal cells. α9 and α10 nAChR subunits were overexpressed in CaSki cells. α*-conotoxins that targeted either α9α10 or α3β4 nAChR were able to significantly inhibit cervical cancer cell proliferation. These findings may provide a basis for new targets for cervical cancer targeted therapy.

Keywords: cell proliferation; cervical cancer; differential expression; nicotinic acetylcholine receptors; α*-conotoxins.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Conotoxins / pharmacology
  • Conotoxins / therapeutic use
  • Conus Snail*
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nicotinic Antagonists / pharmacology*
  • Nicotinic Antagonists / therapeutic use
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / metabolism
  • Receptors, Nicotinic / metabolism*
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • Conotoxins
  • Nicotinic Antagonists
  • Protein Subunits
  • Receptors, Nicotinic
  • alpha-conotoxin TxID, Conus textile
  • alpha-conotoxin, Conus generalis