The Expression Of Peroxisome Proliferator Activated Receptor Alpha (PPARα) In Lung Cancer Tissue And The Inhibitory Effect Of Its Agonist Fenofibrate On Growth Of A549Cell Line Xenograft In Nude Mice

1. The Expression of Peroxisome Proliferator-activated Receptor alpha in Lung Cancer TissuesObjective:To investigate the expression of peroxisome proliferator-activated receptor (PPAR-a) in human lung cancer Methods: Paraffin-embeded tissues from59cases of lung cancer and13cases of non-cancerous lung tissues were stained for the expression of PPAR-a by means of immunohistochemistry.Average OD values were detected by image analysis Results:PPAR-a were expressed in lung cancer and non-cancerous lung tissues, but expression of PPAR-a in non-cancerous lung tissues were higher than that in lung cancer tissues.In4kinds of lung cancer, the sequence of PPARa expression from strong to weak was squamous carcinoma, adenocarcinoma, large-cell lung cancer, small-cell lung cancer;expression of PPAR-a was correlated with histological type,differentiation levels and TNM staging of lung cancer tissues, but not with lymph node metastasis. Conclusion:PPAR-a plays an important role in the pathogenesis and(or) progression of lung cancer,the receptor may serve as a novel therapeutical for treatment of lung cancer in the future.2. Inhibitory effect of PPAR-a agonist Fenofibrate on growth of A549cell line xenograft in nude miceObjective:To investigate inhibitory effects and the mechanism of PPARa agonist Fenofibrate on growth of A549cell line xenograft in nude mice. Methods:The human lung cancer xenograft mode in nude mice was established A549cell, twenty four Balb/c-nu mice with lung cancer xenograft were randomly divided into four groups:control group(A group)、Fenofibrate group(B group)、DDP group(C group)、Fenofibrate+DDP group(D group), observing effects of PPARaagonist Fenofibrate on growth of A549cell line xenograft in nude mice.Immunohistochemistry staining was used for detected the expression of PCNA,CD31;and TUNEL was used to estimate the apoptosis in the tumor tissues,and the expression of PPARa、Caspase-3、Survivin、Bcl-2、NF-κB mRNA and (or) protein in subcutaneous tumors were determined by immunohistochemical method or Western Blot method or RT-PCR. Results:1. After3weeks, the volume of subcutaneous tumors of B,C,D groups were smaller than the control group (P<0.05), especially the combined drugs group decreased significantly than the single drug group; The tumor inhibitory rate of B,C,D group was30.68%、50.88%、61.66%,significant difference in tumor inhibitory rates were found between the treatment groups and the control group(P<0.05).Immunohistochemistry showed that PCNA expression of D group was significantly lower than control group(P<0.01); the expression of C.D31was significantly lower than the control group(P<0.05);cell apoptosis was significantly higher than the control and single drug groups(P<0.05).3. Western Blot results show PPARa protein expression of D group was higher than control group(P<0.01). Immunohistochemistry showed that Bcl-2expression of the treatment groups were significantly lower than the control group, RT-PCR, Western Blot results show expression of mRNA and protein of Caspase-3in the treatment groups were higher than the control group,and mRNA and protein of survivin、protein of NF-κB were lower than the control group,the effect in Combined treatment group was obvious significantly. Conclusion:Fenofibrate could inhibit and enhance inhibition of the growth of xenograft tumor in combination with cisplatin; the possible mechanism is through the activation of PPARa signaling pathway,upregulating the apoptosis protein Caspase-3and downregulation expression of survivin, NF-κB, Bcl-2protein.