PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8

Authors

  • Chuang Yang,

    1. Department of Hepatobiliary Surgery, Mianyang Third People of Hospital, Mianyang 621000, Sichuan Province, Peoples Republic of China
    2. Department of Gastrointestinal Surgery, First Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, Peoples Republic of China
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  • Hai-Zhong Liu,

    1. Department of Gynecology and Obstetrics, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, Peoples Republic of China
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  • Zhong-Xue Fu

    Corresponding author
    1. Department of Hepatobiliary Surgery, Mianyang Third People of Hospital, Mianyang 621000, Sichuan Province, Peoples Republic of China
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To whom correspondence should be addressed (email fzx990521@sina.com).

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.

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