High GSTP1 inhibits cell proliferation by reducing Akt phosphorylation and is associated with a better prognosis in hepatocellular carcinoma

Xiaojia Liu; Ning Tan; Hongtao Liao; Guangdong Pan; Qing Xu; Rong Zhu; Liping Zou; Songqing He; Hongguang Zhu

doi:10.18632/oncotarget.23420

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Research Papers:

High GSTP1 inhibits cell proliferation by reducing Akt phosphorylation and is associated with a better prognosis in hepatocellular carcinoma

Xiaojia Liu, Ning Tan, Hongtao Liao, Guangdong Pan, Qing Xu, Rong Zhu, Liping Zou, Songqing He _ and Hongguang Zhu

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Oncotarget. 2018; 9:8957-8971. https://doi.org/10.18632/oncotarget.23420

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Abstract

Xiaojia Liu1,4*, Ning Tan2,*, Hongtao Liao2, Guangdong Pan3, Qing Xu2, Rong Zhu1, Liping Zou1,4, Songqing He2,5 and Hongguang Zhu1,4

1Department of Pathology, Basic Medical School, Shanghai Medical College, Fudan University, Shanghai 200032, China

2Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin 541001, China

3Department of Hepatobiliary Surgery, The People’s Hospital of Liuzhou, Liuzhou 545001, China

4Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai 200032, China

5Department of Hepatobiliary Surgery, Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

*These authors have contributed equally to this work

Correspondence to:

Songqing He, email: [email protected]

Hongguang Zhu, email: [email protected]

Keywords: hepatocellular carcinoma; GSTP1; prognosis; cell proliferation; Akt

Received: May 10, 2017 Accepted: September 21, 2017 Published: D ecember 19, 2017

ABSTRACT

Glutathione S-transferase (GST) family members promote carcinogenesis and cancer progression. We assessed GST pi 1 (GSTP1) mRNA and protein levels in hepatocellular carcinoma (HCC) using genome databases and tissue microarray (TMA) technology. We found that in cancerous tissues, GSTP1 mRNA was down-regulated in genome databases, and immunohistochemical staining of GSTP1 in 237 HCC cases varied from negative to strongly positive. GSTP1 levels correlated negatively with tumor size and serum alpha-fetoprotein (AFP) in HCC patients, and higher GSTP1 levels associated with longer overall survival (OS) and disease-free survival (DFS). We also found that GSTP1 overexpression restrained HepG2 and Huh7 liver cancer cell proliferation in vivo and in vitro. GSTP1 arrested the cell cycle at G1/S by up-regulating p21 and p27 and down-regulating p-Akt. Interrupting GSTP1 gene expression promoted liver cancer cell proliferation and increased the percentage of cells in S phase by decreasing levels of p21 and p27 and increasing p-Akt. These results suggest high GSTP1 levels provide a better prognosis through suppression of tumorigenesis in HCC.

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Research Papers:

High GSTP1 inhibits cell proliferation by reducing Akt phosphorylation and is associated with a better prognosis in hepatocellular carcinoma

Abstract