Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

J Bras Pneumol. 2013 Nov-Dec;39(6):644-9. doi: 10.1590/S1806-37132013000600002.
[Article in English, Portuguese]

Abstract

Objective: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.

Methods: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied.

Results: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.

Conclusions: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.

OBJETIVO:: Testar a eficácia da combinação terapêutica de antineoplásicos convencionais (cisplatina e etoposídeo) com metformina em linhagem celular NCI-H460 de câncer de pulmão não pequenas células, a fim de desenvolver novas possibilidades terapêuticas com eficácia superior e reduzida toxicidade.

MÉTODOS:: Foi utilizado o ensaio de brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT) e calculado o índice de combinação dos fármacos estudados.

RESULTADOS:: Observamos que o uso de metformina em monoterapia reduziu a viabilidade celular metabólica da linhagem de células estudada. O uso de metformina em combinação com cisplatina ou etoposídeo foi sinérgico e superior à monoterapia com cisplatina ou etoposídeo.

CONCLUSÕES:: A metformina, devido às suas ações independentes em liver kinase B1, apresentou atividade antiproliferativa na linhagem NCI-H460 e, em combinação com cisplatina ou etoposídeo, ampliou a taxa de morte celular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Large Cell / drug therapy
  • Cell Line, Tumor / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology*
  • Drug Combinations
  • Drug Synergism
  • Etoposide / administration & dosage
  • Etoposide / pharmacology*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Metformin / administration & dosage
  • Metformin / pharmacology*

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Drug Combinations
  • Hypoglycemic Agents
  • Etoposide
  • Metformin
  • Cisplatin