PTEN基因在過氧化物酶體增殖物激活受體γ調節肝癌細胞生長中的作用_《中國普外基礎與臨床雜志》

作者：

肖華 , 張峰 , 王學浩

南京醫科大學第一附屬醫院肝臟外科(南京210029);

關鍵詞：

過氧化物酶體增殖物激活受體γ 肝細胞癌 PTEN基因

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　探討過氧化物酶體增殖物激活受體γ（PPARγ）在肝癌細胞生長中的調節作用，以及PTEN和磷酸化蛋白激酶B(pAkt)在該過程中的變化，進一步揭示PPARγ調節肝癌細胞生長的機理。
方法　培養SMMC-7721肝癌細胞，經不同濃度的PPARγ配體15-脫氧-前列腺素J2（15-d-PGJ2）或匹格列酮（pioglitazone）作用不同時間后，用MTT法測定細胞活力，用流式細胞儀進行細胞周期分析，用RT-PCR檢測細胞PTEN mRNA的表達，用Western blot檢測細胞PTEN和pAkt蛋白的表達。
結果　15-d-PGJ2和 pioglitazone對肝癌細胞的增殖均具有抑制作用，且呈時間和劑量依賴性，均能增加G0/G1期細胞的比例，減少S期細胞的比例，增加SMMC-7721細胞PTEN mRNA和蛋白的表達，減少pAkt蛋白的表達。
結論　PPARγ的配體能夠呈時間和劑量依賴性地抑制肝癌細胞的增殖，其機理可能是部分通過上調PTEN的表達而實現的。

引用本文： 肖華,張峰,王學浩. PTEN基因在過氧化物酶體增殖物激活受體γ調節肝癌細胞生長中的作用. 中國普外基礎與臨床雜志, 2007, 14(4): 413-416. doi: 復制

1.	劉江文, 程南生, 潘光棟, 等. PPARγ配體調控人膽囊上皮細胞炎性因子表達的實驗研究 [Ｊ]　. 中國普外基礎與臨床雜志， 2005； 12（4）∶326.
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.	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.
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.	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. 　劉江文, 程南生, 潘光棟, 等. PPARγ配體調控人膽囊上皮細胞炎性因子表達的實驗研究 [Ｊ]　. 中國普外基礎與臨床雜志， 2005； 12（4）∶326.
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. 　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.
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. 　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.

《中國普外基礎與臨床雜志》

PTEN基因在過氧化物酶體增殖物激活受體γ調節肝癌細胞生長中的作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

《中國普外基礎與臨床雜志》

PTEN基因在過氧化物酶體增殖物激活受體γ調節肝癌細胞生長中的作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料