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

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

Oncotarget. 2017 Dec 19;9(10):8957-8971. doi: 10.18632/oncotarget.23420. eCollection 2018 Feb 6.

Authors

Xiaojia Liu^#^{1

2}, Ning Tan^#³, Hongtao Liao³, Guangdong Pan⁴, Qing Xu³, Rong Zhu¹, Liping Zou^{1

2}, Songqing He^{3

5}, Hongguang Zhu^{1

2}

Affiliations

¹ Department of Pathology, Basic Medical School, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai 200032, China.
³ Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin 541001, China.
⁴ Department of Hepatobiliary Surgery, The People's Hospital of Liuzhou, Liuzhou 545001, China.
⁵ Department of Hepatobiliary Surgery, Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

^# Contributed equally.

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.

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