Takei Yuji, Saga Yasushi, Mizukami Hiroaki, Takayama Takeshi, Ohwada Michitaka, Ozawa Keiya, Suzuki Mitsuaki
Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Mol Cancer Ther. 2008 Mar;7(3):704-11. doi: 10.1158/1535-7163.MCT-06-0724.
The main mode of progression of ovarian cancer is peritoneal dissemination, and its inhibition may lead to improved outcome. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) reportedly inhibits the proliferation, migration, and invasion of cancer cells. The purpose of this study is to explore the possibility of PTEN gene therapy for ovarian cancer. We transfected the ovarian cancer cell line SHIN-3 [vascular endothelial growth factor (VEGF)-hypersecretory cell line] with PTEN or luciferase (LUC)-expressing plasmid. After selection, PTEN-overexpressing cells (SHIN-3/PTEN) and control cells (SHIN-3/LUC) were obtained. SHIN-3/PTEN implanted s.c. into nude mice was examined for the change in tumor diameter and the number of new blood vessels. Mice with peritoneally disseminated tumors created by i.p. inoculation of the same cells were examined for changes in body weight and abdominal circumference and for survival time. The growth of s.c. SHIN-3/PTEN was significantly lower than that of control (P < 0.001). Compared with controls, mice with i.p. inoculated SHIN-3/PTEN showed significantly smaller increases in the body weight and abdominal circumference (P < 0.01) and a significantly longer survival time (P < 0.05). VEGF concentration in the supernatant of SHIN-3/PTEN was about half that of controls (P < 0.05). The number of new blood vessels in SHIN-3/PTEN was significantly smaller than that in controls (P < 0.001). Overexpression of PTEN suppressed tumor growth and peritoneal dissemination of VEGF-hypersecretory ovarian cancer cells and prolonged the survival time of the mice with peritoneal disseminated tumor. PTEN gene therapy could have therapeutic potential for ovarian cancer and exerts some of this effect by inhibiting angiogenesis.
卵巢癌的主要进展方式是腹膜播散，抑制这种播散可能会改善预后。据报道，10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）可抑制癌细胞的增殖、迁移和侵袭。本研究的目的是探索PTEN基因治疗卵巢癌的可能性。我们用表达PTEN或荧光素酶（LUC）的质粒转染卵巢癌细胞系SHIN-3[血管内皮生长因子（VEGF）高分泌细胞系]。筛选后，获得了PTEN过表达细胞（SHIN-3/PTEN）和对照细胞（SHIN-3/LUC）。检测皮下接种SHIN-3/PTEN的裸鼠肿瘤直径和新生血管数量的变化。对经腹腔接种相同细胞产生腹膜播散性肿瘤的小鼠，检测其体重、腹围变化及生存时间。皮下接种的SHIN-3/PTEN的生长明显低于对照组（P<0.001）。与对照组相比，经腹腔接种SHIN-3/PTEN的小鼠体重和腹围增加明显较小（P<0.01），生存时间明显更长（P<0.05）。SHIN-3/PTEN上清液中的VEGF浓度约为对照组的一半（P<0.05）。SHIN-3/PTEN中的新生血管数量明显少于对照组（P<0.001）。PTEN的过表达抑制了VEGF高分泌卵巢癌细胞的肿瘤生长和腹膜播散，并延长了腹膜播散性肿瘤小鼠的生存时间。PTEN基因治疗对卵巢癌可能具有治疗潜力，并且通过抑制血管生成发挥部分作用。
