title: PEG-liposomal oxaliplatin combined with nuclear factor-κB inhibitor (PDTC) induces apoptosis in human colorectal cancer cells.
abstract: To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. The aim of the present study was to investigate the effects of polyethylene glycol (PEG)-liposomal oxaliplatin (L-OHP) on the induction of apoptosis in human colorectal cancer SW480 cells and how the nuclear factor-κB (NF-κB) pathway may contribute to mediating PEG-liposomal L-OHP-induced apoptosis. PEG-liposomal L-OHP was prepared and used to treat colorectal cancer SW480 cells. SW480 cell uptake of liposomes was observed by laser focus or SEM. Apoptosis was measured by flow cytometry (FCM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Expression of NF-κB, Bcl-2, Bax and activated caspase-3 (P17) was examined by western blot analyses. The results indicated that PEG-liposomal L-OHP induced apoptosis. When pretreated with pyrrolidine dithiocarbamate (PDTC), PEG-liposomal L-OHP induced a significant apoptotic response. Moreover, apoptosis was associated with concentration of PDTC. Expression of protein p-P65, Bcl-2 was downregulated, but Bax and P17 were upregulated. These findings indicate that PEG-liposomal L-OHP enhances the anticancer potency of the chemotherapeutic agent. Moreover, NF-κB signaling pathways may contribute to mediating PEG-liposomal L-OHP-induced apoptosis.
authors.affiliation: Department of General Surgery, The Third People's Hospital of Mianyang, Mianyang, Sichuan 621000, P.R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhong-Xue
authors.initials: ZX
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D016328:NF-kappa B; D009944:Organoplatinum Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D013859:Thiocarbamates; D051028:bcl-2-Associated X Protein; D000077150:Oxaliplatin; C066229:prolinedithiocarbamate; D011092:Polyethylene Glycols; D011392:Proline; C505407:CASP3 protein, human; D053148:Caspase 3