An experimental study on antitumoral effects of KI-21-3, a synthetic fragment of antimicrobial peptide LL-37, on oral squamous cell carcinoma

J Craniomaxillofac Surg. 2018 Sep;46(9):1586-1592. doi: 10.1016/j.jcms.2018.05.048. Epub 2018 Jun 1.

Abstract

Purpose: The aim of this study was to investigate the oncolytic properties of KI-21-3, a shortened fragment of LL-37, against oral squamous cell carcinoma (OSCC) in an animal model.

Materials and methods: Twelve athymic nude mice were divided into a therapy and a control group of six animals each. In both groups, SCC-4 cells were administered extraorally into the floor of the mouth in order to create an OSCC model. In the study group, KI-21-3 was applied intravenously during the 8th and 9th weeks. The subjects in the control group were injected with phosphate buffered saline solution in the same manner. During an examination period of 12 weeks, weight control was performed twice a week. Tumor growth was further controlled volumetrically via ultrasonography once a week with regular intervals. Following sacrifice, ablated tumoral tissues were immunohistochemically evaluated in order to determine the proliferation and apoptotic properties.

Results: The mean tumor weight in the AMP group was 0.0236 ± 0.023 g, which was 30% lower than the control group with the mean value of 0.01651 ± 0.012 g. In the control group, the approximate number of the proliferating cells per visualized field was fourfold higher compared to the therapy group. Moreover, in the control group, the number of apoptotic cells per visualized field was significantly lower compared to the therapy group.

Conclusion: KI-21-3 showed considerable oncolytic properties on SCC-4 carcinoma cells via antiproliferative and caspase-3 apoptotic pathway. Further investigations are necessary to clarify the dose-dependent effects of this agent.

Keywords: Antimicrobial; Caspase; KI-21-3; Ki-67; LL-37; Peptide.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cathelicidins / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Imaging, Three-Dimensional
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / diagnostic imaging
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Tumor Burden
  • Ultrasonography

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins