• 南京醫(yī)科大學(xué)第一附屬醫(yī)院肝臟外科(南京210029);

目的 　探討過氧化物酶體增殖物激活受體γ（PPARγ）在肝癌細(xì)胞生長(zhǎng)中的調(diào)節(jié)作用，以及PTEN和磷酸化蛋白激酶B(pAkt)在該過程中的變化，進(jìn)一步揭示PPARγ調(diào)節(jié)肝癌細(xì)胞生長(zhǎng)的機(jī)理。
方法 　培養(yǎng)SMMC-7721肝癌細(xì)胞，經(jīng)不同濃度的PPARγ配體15-脫氧-前列腺素J2（15-d-PGJ2）或匹格列酮（pioglitazone）作用不同時(shí)間后，用MTT法測(cè)定細(xì)胞活力，用流式細(xì)胞儀進(jìn)行細(xì)胞周期分析，用RT-PCR檢測(cè)細(xì)胞PTEN mRNA的表達(dá)，用Western blot檢測(cè)細(xì)胞PTEN和pAkt蛋白的表達(dá)。
結(jié)果 　15-d-PGJ2和 pioglitazone對(duì)肝癌細(xì)胞的增殖均具有抑制作用，且呈時(shí)間和劑量依賴性，均能增加G0/G1期細(xì)胞的比例，減少S期細(xì)胞的比例，增加SMMC-7721細(xì)胞PTEN mRNA和蛋白的表達(dá)，減少pAkt蛋白的表達(dá)。
結(jié)論 　PPARγ的配體能夠呈時(shí)間和劑量依賴性地抑制肝癌細(xì)胞的增殖，其機(jī)理可能是部分通過上調(diào)PTEN的表達(dá)而實(shí)現(xiàn)的。

引用本文： 肖華,張峰,王學(xué)浩. PTEN基因在過氧化物酶體增殖物激活受體γ調(diào)節(jié)肝癌細(xì)胞生長(zhǎng)中的作用. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007, 14(4): 413-416. doi: 復(fù)制

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3. 　Valentiner U, Carlsson M, Erttmann R, et al. Ligands for the peroxisome proliferator-activated receptor-gamma have inhibitory effects on growth of human neuroblastoma cells in vitro [Ｊ]　. Toxicology, 2005; 213(1-2)∶157.
4. 　Fenner MH, Elstner E. Peroxisome proliferator-activated receptor-gamma ligands for the treatment of breast cancer [Ｊ]　. Expert Opin Investig Drugs, 2005; 14(6)∶557.
5. 　Lu J, Imamura K, Nomura S, et al. Chemopreventive effect of peroxisome proliferator-activated receptor gamma on gastric carcinogenesis in mice [Ｊ]　. Cancer Res, 2005; 65(11)∶4769.
6. 　Toyoda M, Takagi H, Horiguchi N, et al. A ligand for peroxisome proliferator activated receptor gamma inhibits cell growth and induces apoptosis in human liver cancer cells [Ｊ]　. Gut, 2002; 50(4)∶563.
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8. 　Chen WC, Lin MS, Bai X. Induction of apoptosis in colorectal cancer cells by peroxisome proliferators-activated receptor gamma activation up-regulating PTEN and inhibiting PI3K activity [Ｊ]　. Chin Med J (Engl), 2005; 118(17)∶1477.
9. 　Farrow B, Evers BM. Activation of PPARgamma increases PT-EN expression in pancreatic cancer cells [Ｊ]　. Biochem Biophys Res Commun, 2003; 301(1)∶50.
10. 　Patel L, Pass I, Coxon P, et al. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN [Ｊ]　. Curr Biol, 2001; 11(10)∶764.
11. 　Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway [Ｊ]　. Proc Natl Acad Sci USA, 1999; 96(8)∶4240.
12. 　Leslie NR, Downes CP. PTEN: The down side of PI 3-kinase signalling [Ｊ]　. Cell Signal, 2002; 14(4)∶285.
13. 　Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN [Ｊ]　. Cell, 1998; 95(1)∶29.
14. 　Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics [Ｊ]　. Cancer Res, 2000; 60(6)∶1541.
15. 　Lu Y, Lin YZ, LaPushin R, et al. The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells [Ｊ]　. Oncogene, 1999; 18(50)∶7034.
  1. 1. 　劉江文, 程南生, 潘光棟, 等. PPARγ配體調(diào)控人膽囊上皮細(xì)胞炎性因子表達(dá)的實(shí)驗(yàn)研究 [Ｊ]　. 中國(guó)普外基礎(chǔ)與臨床雜志， 2005； 12（4）∶326.
  2. 2. 　Li M, Lee TW, Mok TS, et al. Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth [Ｊ]　. J Cell Biochem, 2005; 96(4)∶760.
  3. 3. 　Valentiner U, Carlsson M, Erttmann R, et al. Ligands for the peroxisome proliferator-activated receptor-gamma have inhibitory effects on growth of human neuroblastoma cells in vitro [Ｊ]　. Toxicology, 2005; 213(1-2)∶157.
  4. 4. 　Fenner MH, Elstner E. Peroxisome proliferator-activated receptor-gamma ligands for the treatment of breast cancer [Ｊ]　. Expert Opin Investig Drugs, 2005; 14(6)∶557.
  5. 5. 　Lu J, Imamura K, Nomura S, et al. Chemopreventive effect of peroxisome proliferator-activated receptor gamma on gastric carcinogenesis in mice [Ｊ]　. Cancer Res, 2005; 65(11)∶4769.
  6. 6. 　Toyoda M, Takagi H, Horiguchi N, et al. A ligand for peroxisome proliferator activated receptor gamma inhibits cell growth and induces apoptosis in human liver cancer cells [Ｊ]　. Gut, 2002; 50(4)∶563.
  7. 7. 　Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer [Ｊ]　. Science, 1997; 275(5308)∶1943.
  8. 8. 　Chen WC, Lin MS, Bai X. Induction of apoptosis in colorectal cancer cells by peroxisome proliferators-activated receptor gamma activation up-regulating PTEN and inhibiting PI3K activity [Ｊ]　. Chin Med J (Engl), 2005; 118(17)∶1477.
  9. 9. 　Farrow B, Evers BM. Activation of PPARgamma increases PT-EN expression in pancreatic cancer cells [Ｊ]　. Biochem Biophys Res Commun, 2003; 301(1)∶50.
  10. 10. 　Patel L, Pass I, Coxon P, et al. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN [Ｊ]　. Curr Biol, 2001; 11(10)∶764.
  11. 11. 　Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway [Ｊ]　. Proc Natl Acad Sci USA, 1999; 96(8)∶4240.
  12. 12. 　Leslie NR, Downes CP. PTEN: The down side of PI 3-kinase signalling [Ｊ]　. Cell Signal, 2002; 14(4)∶285.
  13. 13. 　Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN [Ｊ]　. Cell, 1998; 95(1)∶29.
  14. 14. 　Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics [Ｊ]　. Cancer Res, 2000; 60(6)∶1541.
  15. 15. 　Lu Y, Lin YZ, LaPushin R, et al. The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells [Ｊ]　. Oncogene, 1999; 18(50)∶7034.