title: PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8.
abstract: Since cellular uptake of PEG [poly(ethylene glycol)]-liposomal L-OHP (oxaliplatin) induces bioactive changes in CRC (colorectal cancer), we have investigated its apoptotic effect and anticancer mechanism. Human CRC SW480 cells were treated with PEG-liposomal L-OHP and a caspase-8 inhibitor [Z-IETD-FMK (benzyloxycarbonyl-Ile-Glu-Thr-dl-Asp-fluoromethylketone)]. Apoptosis was measured by FCM (flow cytometry) and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. Expression of Fas/FasL and cytochrome c was detected using FCM and an immunofluorescence assay. Expression of caspase-8, Bid, caspase-9, caspase-7 and activated caspase-3 (P17) was examined by Western blot analyses. The results indicated that PEG-liposomal L-OHP (28 μg/ml L-OHP) induced marked apoptosis in SW480 cells compared with 28 μg/ml free L-OHP. The expression levels of Fas, FasL, cytochrome c, caspase-9, caspase-7 and activated caspase-3 proteins were up-regulated, with a corresponding increase in apoptosis; however, expression of caspase-8 and Bid were down-regulated as apoptosis increased. When cells were treated with Z-IETD-FMK, apoptosis was inhibited, but there was little impact on the expression of Fas, FasL, cytochrome c, Bid, caspase-9, caspase-7 and activated caspase-3. These findings indicate that PEG-liposomal L-OHP enhances the anticancer potency of the chemotherapeutic agent; moreover, Fas/FasL and caspase-8 signalling pathways play a key role in mediating PEG-liposomal L-OHP-induced apoptosis.
authors: Department of Hepatobiliary Surgery, Mianyang Third People of Hospital, Mianyang 621000, Sichuan Province, People’s Republic of China.
authors: Chuang
authors: C
authors: Yang
authors: Hai-Zhong
authors: HZ
authors: Liu
authors: Zhong-Xue
authors: ZX
authors: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000737:chemistry; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008081:Liposomes; D009944:Organoplatinum Compounds; D019014:fas Receptor; D000077150:Oxaliplatin; D011092:Polyethylene Glycols