Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Yufu-shi, Oita 879-5593, Japan.
Int J Mol Med. 2010 Jan;25(1):97-103.
The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand, facilitates the induction of cell death by a variety of cytotoxic and chemotherapeutic agents in various human tumor cell lines. The purpose of this study was to elucidate the effect of PK11195 on three endometrial cancer cell lines, two ovarian cancer cell lines and normal human endometrial epithelial cells. Endometrial and ovarian cancer cells were treated with various concentrations of PK11195 alone or in combination with chemotherapeutic drugs (cisplatin, paclitaxel), and its effect on cell growth, the cell cycle, apoptosis and related measurements was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed that all endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of PK11195, although normal endometrial epithelial cells were viable after treatment with the same doses of PK11195 that induced growth inhibition in endometrial and ovarian cancer cells. Synergistic anti-neoplastic effects were obtained by a combination of PK11195 with cytostatic drugs. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to apoptosis. These results suggest that PK11195 alone or in combination with chemotherapeutic drugs might be a new therapeutic option for the treatment of endometrial and ovarian cancers.
潜在的抗癌剂 1-(2-氯苯基-N-甲基丙基)-3-异喹啉甲酰胺（PK11195），一种转位蛋白配体，可促进各种细胞毒性和化疗药物在各种人肿瘤细胞系中诱导细胞死亡。本研究的目的是阐明 PK11195 对三种子宫内膜癌细胞系、两种卵巢癌细胞系和正常人类子宫内膜上皮细胞的影响。用不同浓度的 PK11195 单独或与化疗药物（顺铂、紫杉醇）联合处理子宫内膜癌和卵巢癌细胞，研究其对细胞生长、细胞周期、凋亡及相关测量的影响。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法显示，所有子宫内膜癌和卵巢癌细胞系对 PK11195 的生长抑制作用均敏感，尽管用相同剂量的 PK11195 处理后，正常子宫内膜上皮细胞仍存活，但可诱导子宫内膜癌和卵巢癌细胞的生长抑制。PK11195 与细胞抑制剂联合使用可获得协同抗肿瘤作用。通过对外源化磷酯酰丝氨酸的 Annexin V 染色和线粒体跨膜电位的丧失证实诱导凋亡的发生。这种诱导与凋亡相关基因表达的改变同时发生。这些结果表明，PK11195 单独或与化疗药物联合使用可能成为治疗子宫内膜癌和卵巢癌的新治疗选择。
