Effects of PEG-liposomal oxaliplatin on apoptosis, and expression of             Cyclin A and Cyclin D1 in colorectal cancer cells.
Oxaliplatin is one of the agents used against colorectal cancer. Using PEG-liposome encapsulated oxaliplatin may enhance the accumulation of drugs in tumor cells, inducing apoptosis. However, the mechanism of action of PEG-liposome encapsulated oxaliplatin remains unclear. SW480 human colorectal cancer cells were treated with empty PEG-liposomes, free oxaliplatin or PEG-liposomal oxaliplatin. Cell cycle and apoptosis were assessed using fluorescence confocal microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end-labeling (TUNEL). Western blotting was used to analyze the expression of pro-apoptotic, anti-apoptotic and cyclin proteins. We found that PEG-liposomal oxaliplatin induced a stronger apoptotic response than empty PEG-liposomes or free oxaliplatin. Moreover, expression of Cyclin D1 increased, whereas expression of Cyclin A decreased after treatment with PEG-liposomal oxaliplatin. Furthermore, the cell cycle was arrested in the G1 phase. The results presented here indicate that PEG-liposome entrapment of oxaliplatin enhances the anticancer potency of the chemotherapeutic agent. The effect of PEG-liposomal oxaliplatin on apoptosis of SW480 human colorectal cancer cells may be through regulation of expression of Cyclin A or Cyclin D1, as well as pro-apoptotic and anti-apoptotic proteins.
Department of Hepatobiliary Surgery, The Third Hospital of Mianyang, Mianyang, Sichuan 621000, PR China.
Chuang
C
Yang
Hai-Zhong
HZ
Liu
Zhong-Xue
ZX
Fu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms; D019925:Cyclin A / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011092:Polyethylene Glycols
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C530104:CCND1 protein, human; D019925:Cyclin A; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019938:Cyclin D1; D011092:Polyethylene Glycols