RESUMO
Among the most common antitumor drugs used in the treatment of colon cancer are 5-fluorouracil and oxaliplatin (5-FU and OXA). However, both these drugs have many side effects, and hence there is a need for new treatment\approach to reduce the side effects aas well as drug concentration. In this context, here, we investigated the effect of addition of protocatechuic acid (PCA) onto either monotherapies or combination therapies of 5-FU and OXA on the human colon cancer (Caco-2) cell line. In addition, we did evaluate the synergistic effect of PCA with 5-FU and OXA. Further, we determined the suppressive effects of different doses of PCA alone or in combination with 5-FU/OXA on cell proliferation after 24 and 48 hours. We identified a suppressive effect of PCA on cell viability at 48 h starting from the dose of 50 µM Matrix metalloproteinase-2 (MMP-2) and MMP-9 gene expression levels and apoptotic effects showed significant increases and decreases depending on the dose and time applied in the experimental groups. The highest synergistic activity was seen at 2:1 concentration of 5-FU+ PCA. Our findings indicate the presence of the cytotoxic and apoptotic effects of PCA in Caco-2 cells at 48 h, increasing with a dose- and time-dependent manner.
RESUMO
The degeneration of the Lumbar Intervertebral Disc (LIVD) and the other elements of the spine are an inevitable result of aging. However, it is observed that the same degree of degenerative change does not occur in each individual. In the present study, the purpose was to compare the morphometric changes on the lumbar spine with or without intervertebral disc herniation in early period. Group 1 (the Patient Group) consisted of the patients who were diagnosed with lumbar intervertebral disc hernia and who were not operated at least one month clinical duration. Group 2 (the Control Group) consisted of individuals who were selected randomly, had only back pain, underwent magnetic resonance imaging (MRI), and were determined to have intact intervertebral disc. The sagittal and axial MRI sections of lumbar spine was used for measurements and statistical evaluation. There were no statistically significant differences between the intervertebral disc volumes, vertebral body volumes and intervertebral disc anterior and posterior heights of Group 1 and 2 (p>0.05). In terms of anterior-posterior length, the length of the L5 vertebral body was determined to be more in the Patient Group (p<0.05). A correlation was determined in terms of the increase in L2, L4 and L5 volumes with increasing age; however, there were no statistically significant correlations between age increase and a decrease in the intervertebral disc volumes. There were no correlations between the increase in age and the decrease in intervertebral disc heights (p>0.05). There were no apparent relations between the change on the lumbar vertebra corpus and intervertebral disc in early period. It was concluded that the intact intervertebral disc could protect the lower lumbar vertebra corpus from degenerative changes. Although the herniation of the intervertebral disc is newly formed, it is understood that the physiological process or morphometric changes started earlier.
La degeneración del disco intervertebral lumbar y de otros elementos de la columna vertebral son un resultado inevitable del envejecimiento. Sin embargo, no se observa el mismo grado de degeneración en cada individuo. En el presente estudio, el objetivo era comparar los cambios morfométricos en la columna lumbar con o sin hernia de disco intervertebral en el período temprano. El grupo 1 (grupo de pacientes) estaba formado por los pacientes diagnosticados con hernia de disco intervertebral lumbar y que no fueron operados durante al menos un mes. El Grupo 2 (Grupo de Control) consistió en sujetos que fueron seleccionados al azar, reportaban solamente dolor de espalda, fueron sometidos a una resonancia magnética (MRI) y se determinó un disco intervertebral intacto. Las secciones de resonancia magnética sagital y axial de la columna lumbar se utilizaron para las mediciones y la evaluación estadística. No hubo diferencias estadísticamente significativas entre los volúmenes del disco intervertebral, los volúmenes del cuerpo vertebral y las alturas anterior y posterior del disco intervertebral de los Grupos 1 y 2 (p> 0,05). En términos de longitud anterior-posterior, se determinó que la longitud del cuerpo vertebral L5 era mayor en el grupo de pacientes (p <0,05). Se determinó una correlación en términos del aumento en los volúmenes L2, L4 y L5 con el aumento de la edad; sin embargo, no hubo correlaciones estadísticamente significativas entre el aumento de la edad y una disminución en los volúmenes del disco intervertebral. No hubo correlaciones entre el aumento de la edad y la disminución de las alturas de los discos intervertebrales (p> 0,05). No hubo relaciones aparentes entre el cambio en el cuerpo de la vértebra lumbar y el disco intervertebral en el período temprano. Se concluyó que el disco intervertebral intacto podría proteger el cuerpo de la vértebra lumbar inferior de los cambios degenerativos. Aun cuando la formación de la hernia del disco fue reciente, se entiende que el proceso fisiológico o los cambios morfométricos habían comenzado antes.