1,25-Dihydroxyvitamin D3 Treatment Shrinks Uterine Leiomyoma Tumors in the Eker Rat Model
1,25-Dihydroxyvitamin D3 Treatment Shrinks Uterine Leiomyoma Tumors in the Eker Rat Model
复制标题
DOI：
10.1095/biolreprod.111.098145
复制
发表时间：
2012-04-01
影响因子：
3.6
通讯作者：
Al-Hendy, Ayman
中科院分区：
文献类型：
--
作者：
Halder, Sunil K.;Sharan, Chakradhari;Al-Hendy, Ayman
子宫平滑肌瘤（肌瘤）是育龄妇女最常见的良性肿瘤。这些肿瘤在非裔美国妇女中的发病率是白人妇女的三到四倍，她们患维生素D缺乏症的发病率也是白人妇女的10倍。最近的研究表明1,25-二羟基维生素D3对几种癌症有抗肿瘤作用，但其对子宫平滑肌瘤的作用尚不清楚。为了研究1,25-二羟维生素D3对子宫平滑肌瘤的抗肿瘤和治疗作用，将14-16月龄子宫平滑肌瘤雌性Eker大鼠随机分为对照组和实验组，分别皮下注射1,25-二羟维生素D3 (0.5 μ g/kg / d) 3周。实验结束时，将大鼠安乐死，并对平滑肌瘤肿瘤进行分析。1,25-二羟基维生素D3治疗可显著减少Eker大鼠的平滑肌瘤肿瘤大小。它还通过抑制细胞生长和增殖相关基因（Pcna、cyclin D1 [Ccnd1]、Myc、Cdk1、Cdk2和Cdk4）、抗凋亡基因（Bcl2和Bcl2l1 [Bcl-x]）以及雌激素和孕激素受体来减小平滑肌瘤的大小。此外，免疫组织化学显示1,25-二羟基维生素d3治疗的Eker大鼠平滑肌瘤中PCNA和MKI67（增殖标志物）的表达降低，caspase 3的表达增加。血清毒性分析显示，1,25-二羟基维生素d3处理和对照Eker大鼠的SGOT、SGPT、钙和总胆红素水平相似。这些结果支持1,25-二羟基维生素D3是一种抗肿瘤药物，可能是治疗子宫平滑肌瘤的一种潜在的安全、非手术治疗选择。
Uterine leiomyomas (fibroids) are the most common benign tumors in women of reproductive age. These tumors are three to four times more prevalent in African American women, who also have a 10 times higher incidence of hypovitaminosis D than white women. Recent studies have demonstrated the antitumor effects of 1,25-dihydroxyvitamin D3 on several cancers, but its effects on uterine leiomyomas are still unknown. To determine the antitumor and therapeutic effects of 1,25-dihydroxyvitamin D3 on uterine leiomyomas, female Eker rats (14-16 mo old) harboring uterine leiomyomas were randomized into control and experimental groups and were given vehicle versus 1,25-dihydroxyvitamin D3 (0.5 mu g/kg per day) subcutaneously for 3 wk, respectively. At the end of the experiment, the rats were euthanized, and the leiomyoma tumors were analyzed. Treatment with 1,25-dihydroxyvitamin D3 significantly reduced leiomyoma tumor size in Eker rats. It also reduced leiomyoma size by suppressing cell growth and proliferation-related genes (Pcna, cyclin D1 [Ccnd1], Myc, Cdk1, Cdk2, and Cdk4), antiapoptotic genes (Bcl2 and Bcl2l1 [Bcl-x]), and estrogen and progesterone receptors. Additionally, immunohistochemistry revealed decreased expression of PCNA and MKI67 (a marker of proliferation) and increased expression of caspase 3 in 1,25-dihydroxyvitamin D3-treated Eker rat leiomyomas. Toxicity analyses using serum samples showed similar levels of SGOT, SGPT, calcium, and total bilirubin in 1,25-dihydroxyvitamin D3-treated and vehicle-treated control Eker rats. These results support that 1,25-dihydroxyvitamin D3 is an antitumor agent that may be a potential safe, nonsurgical therapeutic option for the treatment of uterine leiomyomas.