title: A novel combination of TRAIL and doxorubicin enhances antitumor effect based on passive tumor-targeting of liposomes.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Liangran
authors.initials: L
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ren
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Yulong
authors.initials: Y
authors.lastname: Ren
authors.forename: Jingwei
authors.initials: J
authors.lastname: Li
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Wen
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005453:Fluorescence; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D013010:Sonication; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D053221:TNF-Related Apoptosis-Inducing Ligand; D004317:Doxorubicin