Effect of PTEN Gene in Regulation of Growth of Hepatocellular Carcinoma Cells by PPARγ_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XIAO Hua , ZHANG Feng , WANG Xuehao

Department of Hepatic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;

Corresponding author：

Keywords：

Peroxisome proliferators-activated receptor gamma; Hepatocellular carcinoma; PTEN gene

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Objective 　To study the effects of peroxisome proliferators-activated receptor (PPAR) γ on the growth of human hepatocellular carcinoma cells and explore the roles of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and phospho-Akt in this process.
Methods 　SMMC-7721 cells were treated with 15-d-PGJ2 or pioglitazone, which were two kinds of PPARγ ligands, at different concentrations. The viability of SMMC-7721 cells was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. PTEN mRNA level was determined by RT-PCR. The protein expressions of PTEN and pAkt were measured by Western blot analysis.
Results 　It was demonstrated through MTT assay that both 15-d-PGJ2 and pioglitazone had an inhibitory effect on the growth of SMMC-7721 cells in a time- and dose- dependent manner. According to flow cytometry detection, more cells were arrested in G0/G1 phase. Increased expression of PTEN mRNA was detected in 15-d-PGJ2 or pioglitazone-treated cells through RT-PCR. Increased expression of PTEN protein and decreased expression of pAkt were confirmed by Western blot analysis.
Conclusion 　The ligands of PPARγ could inhibit SMMC-7721 cells proliferation in a time- and dose- dependent manner. The upregulation of PTEN may be involved in the underlying mechanism.

Citation： XIAO Hua,ZHANG Feng,WANG Xuehao. Effect of PTEN Gene in Regulation of Growth of Hepatocellular Carcinoma Cells by PPARγ. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 413-416. doi: Copy

1.	刘江文, 程南生, 潘光栋, 等. PPARγ配体调控人胆囊上皮细胞炎性因子表达的实验研究 [Ｊ]　. 中国普外基础与临床杂志， 2005； 12（4）∶326.
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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.
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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. 　刘江文, 程南生, 潘光栋, 等. PPARγ配体调控人胆囊上皮细胞炎性因子表达的实验研究 [Ｊ]　. 中国普外基础与临床杂志， 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of PTEN Gene in Regulation of Growth of Hepatocellular Carcinoma Cells by PPARγ

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