Milam Michael R, Celestino Joseph, Wu Weiguo, Broaddus Russell R, Schmeler Kathleen M, Slomovitz Brian M, Soliman Pamela T, Gershenson David M, Wang Hong, Ellenson Lora H, Lu Karen H
Department of Gynecologic Oncology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Am J Obstet Gynecol. 2007 Mar;196(3):247.e1-5. doi: 10.1016/j.ajog.2006.10.872.
Phosphatase and tensin homolog (PTEN) mutations are associated with human endometrial cancers, and PTEN heterozygote(+/-) mice have a high rate of endometrial neoplasia. The objective of this study was to evaluate an oral mTOR inhibitor (mTOR-I) on the reduction of endometrial hyperplasia in an animal model.
Three groups of 10 female mice were treated from age 20-26 weeks: group A, Pten wild type with mTOR-I; group B, Pten+/- with placebo; and group C, Pten +/- with mTOR-I. Rates of hyperplasia and markers of proliferation and apoptosis were evaluated.
Higher grade hyperplasia occurred in a significantly greater percentage of the untreated Pten+/- group B (80%; 8/10) compared with groups A (0%; 0/10) and C (20%; 2/10; P < .02). The treated Pten+/- mTOR-I group C also demonstrated significantly increased apoptosis (P < .002) and decreased proliferation index (P < .02) compared with the untreated group B.
Oral mTOR inhibition decreases the progression of endometrial hyperplasia in the Pten heterozygote murine model through decreased cell proliferation and increased apoptosis.
磷酸酶和张力蛋白同源物（PTEN）突变与人类子宫内膜癌相关，PTEN杂合子（+/-）小鼠有较高的子宫内膜肿瘤发生率。本研究的目的是评估一种口服雷帕霉素靶蛋白抑制剂（mTOR-I）在动物模型中对子宫内膜增生的减轻作用。
将三组各10只雌性小鼠从20至26周龄开始进行处理：A组，Pten野生型小鼠给予mTOR-I；B组，Pten+/-小鼠给予安慰剂；C组，Pten+/-小鼠给予mTOR-I。评估增生率以及增殖和凋亡标志物。
与A组（0%；0/10）和C组（20%；2/10）相比，未处理的Pten+/-的B组出现高级别增生的比例显著更高（80%；8/10）（P < .02）。与未处理的B组相比，经处理的Pten+/- mTOR-I的C组也显示凋亡显著增加（P < .002），增殖指数降低（P < .02）。
口服mTOR抑制可通过减少细胞增殖和增加凋亡来降低Pten杂合子小鼠模型中子宫内膜增生的进展。
