Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Nanotechnology. 2011 Jul 1;22(26):265105. doi: 10.1088/0957-4484/22/26/265105. Epub 2011 May 18.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel anticancer agent for non-small cell lung cancer (NSCLC). However, approximately half of NSCLC cell lines are highly resistant to TRAIL. Doxorubicin (DOX) can sensitize NSCLC cells to TRAIL-induced apoptosis, indicating the possibility of combination therapy. Unfortunately, the therapeutic effect of a DOX and TRAIL combination is limited by multiple factors including the short serum half-life of TRAIL, poor compliance and application difficulty in the clinic, chronic DOX-induced cardiac toxicity, and the multidrug resistance (MDR) property of NSCLC cells. To solve such problems, we developed the combination of TRAIL liposomes (TRAIL-LP) and DOX liposomes (DOX-LP). An in vitro cytotoxicity study indicated that DOX-LP sensitized the NSCLC cell line A-549 to TRAIL-LP-induced apoptosis. Furthermore, this combination therapy of TRAIL-LP and DOX-LP displayed a stronger antitumor effect on NSCLC in xenografted mice when compared with free drugs or liposomal drugs alone. Therefore, the TRAIL-LP and DOX-LP combination therapy has excellent potential to become a new therapeutic approach for patients with advanced NSCLC.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种新型的非小细胞肺癌（NSCLC）抗癌药物。然而，大约一半的 NSCLC 细胞系对 TRAIL 具有高度耐药性。多柔比星（DOX）可以使 NSCLC 细胞对 TRAIL 诱导的细胞凋亡敏感，表明联合治疗的可能性。不幸的是，DOX 和 TRAIL 联合治疗的疗效受到多种因素的限制，包括 TRAIL 的血清半衰期短、顺应性差以及在临床上应用困难、慢性 DOX 诱导的心脏毒性和 NSCLC 细胞的多药耐药（MDR）特性。为了解决这些问题，我们开发了 TRAIL 脂质体（TRAIL-LP）和 DOX 脂质体（DOX-LP）的联合治疗。体外细胞毒性研究表明，DOX-LP 使 NSCLC 细胞系 A-549 对 TRAIL-LP 诱导的细胞凋亡敏感。此外，与游离药物或脂质体药物单独使用相比，TRAIL-LP 和 DOX-LP 的联合治疗对荷瘤小鼠的 NSCLC 具有更强的抗肿瘤作用。因此，TRAIL-LP 和 DOX-LP 联合治疗具有成为晚期 NSCLC 患者新治疗方法的巨大潜力。
