Effects Of The Tamoxifen-Treatment And P53 Adenovirus Transfection On The P53 Expression And Cell Cycle In Keloid Fibroblasts

Kloid represents a kind of pathological overhealing process, which is typical of spreading out of primary wound range. Keloid scars can be not only aesthetically disfiguring, but also severely disabling. Histologically, it is a kind of benign tumor characterized as abnormal proliferation of fibroblasts. Unfortunately, existing treatments are of unsuccessful.Tamoxifen, a synthetic nonsteroidal antiestrogen, has been used extensively for the treatment of breast cancer. Pharmacological effects of tamoxifen include the alteration of mRNA transcriptional synthesis, decrease of cellular proliferation, ceasing of cell cycle in the G1 phase. In addition, there are accumulating data to suggest that tamoxifen may be helpful in treating abnormal proliferative healing disorders. Furthermore, tamoxifen has been demonstrated to decrease the process of proliferation of both normal dermal and keloid fibroblasts, as well as the synthesis of collagen.p53 is a kind of anti-cancer gene which has been shown to play an important role in modulation of cell proliferation. The aim of this experiment is to evaluate the effect of the tamoxifen-Treatment and p53 Adenovirus Transfection on the p53 Expression and Cell Cycle in Keloid Fibroblasts and its mechanism.[Objective] Fibroblasts from kloids of 6 patients were collected and only 6-10 passages of cultured fibroblasts were selected for the expriment.â‘ To construct the adenoviral vector p53 system.â‘¡To examine the stimulative effects of tamoxifen and adenoviral vector p53 on the change of p53mRNA expression, P53 protein expression and cell cycle of cultured keloid fibroblasts.â‘¢To elucidate the relationship between p53 expression and cell cycle of cultured keloid fibroblasts.â‘£To investigate whether there is coherent inhibitory effect between the tamoxifen and the adenoviral vector p53 system.[Methods] â‘ The adenoviral vector p53 system was constructed and transfected to kloid fibroblast.â‘¡The derived cells were divided into four groups.The p53mRNA expression and its protein production were detected by RT-PCR and Western Blot after the use of tamoxifen and/or adenoviral vector p53. â‘¢The variations of cell cycle wereanalyzed with the help of flow cytometer.[Results] *The adenoviral vector p53 system was constructed and transfected to fibroblasts successfully. * Compared to that of control group, the p53mRNA expression and P53 protein production increased significantly within 3 days after tamoxifen and adenoviral vector p53 used. Correspondingly, the cell growth was inhibited and a large percent of fibroblasts derived from keloids was distributed in GO and G1 stage. *After tamoxifen and adenoviral vector p53 used simutaneously, the p53 mRNA expression and P53 protein expression increased more significantly than that in the use of tamoxifen and adenoviral vector p53 separately. [Conclusion] Both use of tamoxifen and adenoviral vector p53 system can increase the p53mRNA expression and P53 protein production significantly and lead to the inhibition of the keloid fibroblasts growth. There is coherent inhibitory effect between the use of tamoxifen and adenoviral vector p53.