Dys-psychological Stress Effect on Expressions of P53 and NFκBp65 in Human Ovarian Carcinoma In Vivo

Objective： To investigate the dys-psychological stress effect on the growth of subcutaneous xenotransplanted tumor in nude mice bearing human epithelium ovarian carcinoma, and the influence on P53 and NFκBp65 expressions. Methods： The subcutaneous tumor xenografts were established by implanting human epithelium ovarian carcinoma tissues into nude mice and the dys-psychological stress model was established with restraint. The mice were randomized into the following four treatment groups with each group six mice respectively： tumor group （group A）, normal saline intraperitoneal injection; tumor with stress group （group B）, normal saline intraperitoneal injection; tumor therapy group （group C）, cisplatin intraperitoneal injection; and tumor therapy with stress group （group D）, cisplatin intraperitoneal injection. The expressions of P53 and NFκBp65 in tumor tissues were determined by Western blotting. Results： The expressions of P53 and NFκBp65 in each restraint group were enhanced compared with the control groups （P0.05）. Conclusion： The dys-psychological stress may induce the high expressions of P53 and NFκBp65 proteins and further promote tumor growth.

Small Interfering RNA Targeting MDR1 Inhibits Ovarian Cancer Growth and Increases Efficacy of Chemotherapy in vivo

Objective： To further validate a knockdown approach for circumventing the multidrug resistance gene （MDR1）, we used small interfering RNA（siRNA） targeting MDR1 gene to inhibit the expression of MDR1 gene and P-glycoprotein（P-gp） in vivo. Methods： Ascite tumor xenografts were established by implanting human ovarian carcinoma cells SKOV3/AR intraperitoneally into the nude mice. The mice were randomized into the following three treatment groups with each group six mice respectively： Taxol, Taxol with lipofectamine and Taxol with siRNA/MDR1- lipofectamine intraperitoneal injection. The tumor growth rate and the ascite growth rate of mice were investigated. The expressions of MDR1 gene and P-gp in mice were determined by reverse transcription-polymerase chain reaction（RT-PCR） and immunohistochemistry respctively. Results： The growth of tumors and ascites in mice treated with Taxol and siRNA/MDR1- lipofectamine was significantly inhibited compared with those in mice of other groups. After 28 days＇ treatment, the average tumor weight and ascite volume decreased by 43.6% and 29.7% in the group treated with Taxol and siRNA/MDRl-lipofectamine compared with these treated with Taxol alone （P〈0.001）. The expressions of MDR1 gene and P-gp in the group treated with Taxol and siRNA/MDRl-lipofectamine were also decreased compared with those in the group treated with Taxol alone （P〈0.001）. Conclusion： Small interfering RNA targeting-MDR1 can effectively and specifically suppress the expression of MDRl（P-glycoprotein） and inhibit ovarian cancer growth in vivo.