γ-Glutamylcyclotransferase Knockdown Inhibits Growth of Lung Cancer Cells Through G0/G1 Phase Arrest.
Lung cancer as an aggressive type tumor is rapidly growing and has become the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and lung cancer, GGCT expression in human lung cancer cell lines was first determined by real-time quantitative PCR and western blot. GGCT is expressed in all tested lung cancer cell lines, A549, H1299, and H460. Then, a lentivirus-based system was applied to knock down GGCT in A549 cells, which were thus divided into Lv-shGGCT, Lv-shCon, and Con (noninfected) groups. Methylthiazol tetrazolium assay showed that the cell proliferation was decreased by over 50% in the Lv-shGGCT group compared with controls. The size and number of colonies were dramatically reduced in the GGCT knockdown group, as measured by colony formation assay. Moreover, A549 cells infected with Lv-shGGCT were arrested in the G0/G1 phase as assayed by flow cytometry. Furthermore, the expression levels of CDK4, CDK6, and cyclin D1 were decreased and the cleaved level of PARP was increased in GGCT knockdown cells. In conclusion, GGCT plays a critical role in lung cancer cell proliferation and may be a potential cancer therapeutic target.
1 Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University , Shanghai, China .
Zhifeng
Z
Lin
2 Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University , Shanghai, China .
Liwen
L
Xiong
1 Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University , Shanghai, China .
Jianhua
J
Zhou
1 Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University , Shanghai, China .
Jin
J
Wang
3 Department of Medicine, Shanghai Jiaotong University , Shanghai, China .
Zhao
Z
Li
1 Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University , Shanghai, China .
Haiyang
H
Hu
1 Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University , Shanghai, China .
Qiang
Q
Lin
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003114:Colony-Forming Units Assay; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D005722:gamma-Glutamylcyclotransferase / Q000235:genetics* / Q000378:metabolism
D019938:Cyclin D1; D011065:Poly(ADP-ribose) Polymerases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D005722:gamma-Glutamylcyclotransferase
RNA interference; cell cycle; knockdown; lung cancer; proliferation; γ-glutamylcyclotransferase