Novel therapeutic regimens for urethane-induced early lung cancer in rats: Combined cisplatin nanoparticles with vitamin-D3

IUBMB Life. 2021 Feb;73(2):362-374. doi: 10.1002/iub.2432. Epub 2020 Dec 17.

Abstract

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.

Keywords: cisplatin; lung cancer; nanoparticles; urethane; vitamin-D3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Carcinogens / toxicity
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / pharmacology*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology*
  • Disease Models, Animal*
  • Drug Therapy, Combination
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Urethane / toxicity*
  • Vitamins / administration & dosage
  • Vitamins / pharmacology

Substances

  • Antineoplastic Agents
  • Carcinogens
  • Vitamins
  • Cholecalciferol
  • Urethane
  • Cisplatin