Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, China.
Biochem Biophys Res Commun. 2013 Jun 7;435(3):385-90. doi: 10.1016/j.bbrc.2013.04.097. Epub 2013 May 9.
Epithelial ovarian cancer (EOC) is one of the leading causes of gynecological cancer death. Approximately 70% of the patients experience recurrence accompanied by the development of drug resistance 2-3 years after chemotherapy. Picropodophyllin (PPP) is a newly identified insulin-like growth factor-1 receptor (IGF-1R) inhibitor that has been shown to have anticancer properties. In this study, we investigated the effect of PPP on EOC growth in vitro and in vivo. The EOC cell line SKOV-3 was treated with increasing concentrations of PPP or cisplatin, and cell viability and apoptosis were evaluated. To study the effects of PPP on EOC growth, apoptosis, and toxicity in vivo, a BALB/c nude mouse xenograft model was established. Mice were treated with normal saline (controls), PPP, cisplatin, or PPP in combination with cisplatin. In addition, the expression of phosphorylated IGF-1R (pIGF-1R) was examined in vitro and in vivo. PPP induced a dose-dependent decrease in SKOV-3 cell viability in vitro and reduced tumor volume and weight in the in vivo xenograft model. Furthermore, PPP in combination with cisplatin was more effective in inhibiting the growth of SKOV-3 cells and xenografts than either drug alone. PPP-mediated growth inhibition was associated with apoptosis induction in vitro and in vivo. PPP was well tolerated in vivo and exerted its effects with minimal hepatotoxicity and renal toxicity. PPP downregulated the expression of pIGF-1R in vitro and in vivo, an effect that appeared to be associated with its growth inhibitory properties. Our results indicate that PPP may have therapeutic application in the treatment of EOC.
上皮性卵巢癌（EOC）是妇科癌症死亡的主要原因之一。大约 70%的患者在化疗后 2-3 年内经历复发，并伴有耐药性的发展。鬼臼毒素（PPP）是一种新发现的胰岛素样生长因子-1 受体（IGF-1R）抑制剂，已显示出抗癌特性。在这项研究中，我们研究了 PPP 对体外和体内 EOC 生长的影响。用递增浓度的 PPP 或顺铂处理 EOC 细胞系 SKOV-3，并评估细胞活力和细胞凋亡。为了研究 PPP 对 EOC 生长、凋亡和体内毒性的影响，建立了 BALB/c 裸鼠异种移植模型。用生理盐水（对照）、PPP、顺铂或 PPP 联合顺铂处理小鼠。此外，还检查了体外和体内磷酸化 IGF-1R（pIGF-1R）的表达。PPP 在体外诱导 SKOV-3 细胞活力呈剂量依赖性下降，并减少体内异种移植模型中的肿瘤体积和重量。此外，PPP 联合顺铂在抑制 SKOV-3 细胞和异种移植生长方面比单独使用任何一种药物都更有效。PPP 介导的生长抑制与体外和体内的细胞凋亡诱导有关。PPP 在体内耐受性良好，具有最小的肝毒性和肾毒性。PPP 下调了体外和体内 pIGF-1R 的表达，这种作用似乎与其生长抑制特性有关。我们的结果表明，PPP 可能在治疗 EOC 方面具有治疗应用。
