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. .
Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Etoposide/pharmacology , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents/administration & dosage , Cell Survival , Carcinoma, Large Cell/drug therapy , Cell Line, Tumor/metabolism , Cell Proliferation/drug effects , Cisplatin/administration & dosage , Drug Combinations , Drug Synergism , Etoposide/administration & dosage , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosageABSTRACT
El cáncer de pulmón en forma de tumor de Pancoast afecta a unos 200 cubanos anualmente y es todavía considerado incurable por muchos en Cuba. En el Instituto Nacional de Oncología y Radiobiología se realizó un estudio prospectivo de introducción tecnológica, que consistió en radio-quimioterapia preoperatoria y cirugía ampliada, aplicadas a pacientes con cáncer de pulmón en forma de tumor de Pancoast en etapa potencialmente curable. Entre enero de 1991 y marzo de 2004 se incluyeron 36 pacientes (28 hombres, 8 mujeres, con edad promedio de 51,6 años, mínima de 34 y máxima de 69). Los tipos celulares fueron: adenocarcinoma (21), epidermoide (12), carcinoma de células grandes (2), carcinoma indiferenciado (1). Hubo 28 casos en etapas IIB, 4 en etapa IIIA y 4 en etapa IIIB. Ocurrieron 3 muertes quirúrgicas no relacionadas con la técnica operatoria. La supervivencia a los 3 y 5 años fue de 57 por ciento y 38 por ciento, respectivamente. El tratamiento combinado de radio-quimioterapia y cirugía ampliada logra el control loco-regional y la supervivencia prolongada en muchos pacientes con tumor de Pancoast en etapa localizada(AU)
The lung cancer in form of tumor of Pancoast affects about 200 Cubans annually and it is still considered incurable for many in Cuba. In the National Institute of Oncología and Radiobiología he/she was carried out a prospective study of technological introduction that consisted on radio-chemotherapy preoperatoria and enlarged surgery, applied to patient with lung cancer in form of tumor of Pancoast in stage potentially curable. Between January of 1991 and March of 2004 36 patients were included (28 men, 8 women, with age 51,6 year-old average, minimum of 34 and maxim of 69). The cellular types were: adenocarcinoma (21), epidermoide (12), carcinoma of big cells (2), carcinoma indiferenciado (1). there were 28 cases in stages IIB, 4 in stage IIIA and 4 in stage IIIB. They not happened 3 surgical deaths related with the operative technique. The survival to the 3 and 5 years was of 57 percent and 38 percent, respectively. The combined treatment of radio-chemotherapy and enlarged surgery achieves the crazy-regional control and the survival prolonged in many patients with tumor of Pancoast in located stage(AU)