Intervention effects of nedaplatin and cisplatin on proliferation and apoptosis of human tumour cells in vitro

Asian Pac J Cancer Prev. 2012;13(9):4531-6. doi: 10.7314/apjcp.2012.13.9.4531.

Abstract

Objective: To study synergistic effects of nedaplatin and cisplatin on three human carcinoma cell lines (esophageal carcinoma cell line Eca-109, ovarian carcinoma Skov-3 and cervical carcinoma Hela).

Methods: Inhibition effects were evaluated by MTT assay and cell apoptosis was detected by flow cytometry. In addition, changes of Ki-67, Bax and Bcl-2 at mRNA and protein levels were quantified by RT-PCR and Western blotting.

Results: Growth inhibition in each cell lines was dose-dependent after exposure to nedaplatin or cisplatin alone. The interaction of the two drugs was synergistic at higher concentrations according to the median-effect principle. The inhibition rates with nedaplatin, cisplatin and combined treatment were 41.9±4.1%, 47.4±2.9%, 52.5±0.9%(Eca-109), 39.0±1.26%, 45.0±1.45% , 56.2±1.44% (Skov-3) and 44.8±2.11%, 46.9±0.99%, 56.6±1.83% (Hela) respectively, with increase in apoptosis. Compared with the nedaplatin or cisplatin alone treatment group, the combinative treatment group's Ki-67 and bcl-2 mRNA (protein) expression was decreased while that of Bax mRNA (protein) was increased.

Conclusion: Compared to the effects of nedaplatin or cisplatin alone at high concentrations, combination of nedaplatin and cisplatin at low concentrations proved to be much more effective for inhibition of proliferation and the induction of apoptosis in the Eca-109, Skov-3 and Hela cell lines.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma / drug therapy*
  • Cell Proliferation / drug effects*
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Esophageal Neoplasms / drug therapy*
  • Female
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Organoplatinum Compounds / pharmacology*
  • Ovarian Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • Ki-67 Antigen
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • nedaplatin
  • Cisplatin