Ikemoto Keisuke, Shimizu Kosuke, Ohashi Kento, Takeuchi Yoshihito, Shimizu Motohiro, Oku Naoto
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Sugiyama Chemical and Industrial Laboratory, Yokohama, Japan.
Cancer Sci. 2016 Jan;107(1):53-9. doi: 10.1111/cas.12839. Epub 2015 Dec 11.
Bauhinia purprea agglutinin (BPA) is a well-known lectin that recognizes galactosyl glycoproteins and glycolipids. In the present study, we firstly found that BPA bound to human prostate cancer specimens but not to normal prostate ones. Therefore, we sought to develop BPA-PEG-modified liposomes (BPA-PEG-LP) encapsulating anticancer drugs for the treatment of prostate cancer. We examined the tumor targetability of BPA-PEG-LP with human prostate cancer DU145 cells, and observed that fluorescently labeled BPA-PEG-LP dominantly associated with the cells via the interaction between liposome-surface BPA and cell-surface galactosyl molecules. We also observed that BPA-PEG-LP accumulated in the prostate cancer tissue after the i.v. injection to DU145 solid cancer-bearing mice, and strongly bound to the cancer cells. In a therapeutic study, DU145 solid cancer-bearing mice were i.v. injected thrice with BPA-PEG-LP encapsulating doxorubicin (BPA-PEG-LPDOX, 2 mg/kg/day as the DOX dosage) or PEG-modified liposomes encapsulating DOX (PEG-LPDOX). As a result, BPA-PEG-LPDOX significantly suppressed the growth of the DU145 cancer cells, whereas PEG-LPDOX at the same dosage as DOX showed little anti-cancer effect. The present study suggested that BPA-PEG-LP could be a useful drug carrier for the treatment of human prostate cancers.
紫羊蹄甲凝集素(BPA)是一种著名的凝集素,可识别半乳糖基糖蛋白和糖脂。在本研究中,我们首先发现BPA与人类前列腺癌标本结合,但不与正常前列腺标本结合。因此,我们试图开发包裹抗癌药物的BPA-聚乙二醇修饰脂质体(BPA-PEG-LP)用于治疗前列腺癌。我们用人类前列腺癌DU145细胞检测了BPA-PEG-LP的肿瘤靶向性,观察到荧光标记的BPA-PEG-LP通过脂质体表面的BPA与细胞表面半乳糖基分子之间的相互作用主要与细胞结合。我们还观察到,在给荷DU145实体癌小鼠静脉注射后,BPA-PEG-LP在前列腺癌组织中蓄积,并与癌细胞强烈结合。在一项治疗研究中,给荷DU145实体癌小鼠静脉注射三次包裹阿霉素的BPA-PEG-LP(BPA-PEG-LPDOX,阿霉素剂量为2mg/kg/天)或包裹阿霉素的聚乙二醇修饰脂质体(PEG-LPDOX)。结果,BPA-PEG-LPDOX显著抑制了DU145癌细胞的生长,而相同阿霉素剂量的PEG-LPDOX几乎没有抗癌作用。本研究表明,BPA-PEG-LP可能是治疗人类前列腺癌的一种有用的药物载体。