Celecoxib Inhibits Hepatocellular Carcinoma Cell Growth and Migration by Targeting PNO1.

Abstract

BACKGROUND Celecoxib has shown anti-tumor activities against several types of cancer. Although the majority of research focuses on its mechanism via cyclooxygenase-2 (COX-2) enzyme inhibition, we identified a distinct mechanism behind celecoxib anti-cancer abilities. MATERIAL AND METHODS We treated hepatocellular carcinoma (HCC) Huh-7 cells and tumor xenograft mice models with celecoxib to test its effects on the tumor. Using gene chip method to identify the differential expressed genes after celecoxib treatment and using pathway enrichment analysis to predict the potential pathways for further study. We transfected cells with lentiviral shRNA to detect the effect of RNA binding gene partner of NOB1 (PNO1) on tumor growth in vitro and in vivo. Further we performed western blot to detect the effect of PNO1 on the protein kinase B (AKT) pathway. RESULTS Celecoxib inhibited HCC cell growth in vitro and in vivo, and gene chip and pathway enrichment analysis revealed that PNO1 may be the potential target of celecoxib in HCC cells. Celecoxib significantly reduced levels of PNO1 in tumor tissue. Knockdown of PNO1 remarkably suppressed tumor growth and metastasis in vitro and in vivo. Disruption of PNO1 expression significantly reduced protein kinase B (AKT)/rapamycin (mTOR) signaling, indicating that this pathway may be involved in PNO1-mediated tumorigenic activity. CONCLUSIONS Celecoxib may exert its anti-tumor activity by inhibiting PNO1, and that AKT/mTOR signaling helps mediate the oncogenic effects of PNO1. This work offers the first evidence for a role of PNO1 as an HCC oncogene, which may open new avenues for prevention and treatment of HCC.

• Authors: Huijun Dai, Suisui Zhang, Riliang Ma, Linghui Pan
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 25 Pg. 7351-7360 (Sep 30 2019) ISSN: 1643-3750 [Electronic] United States
• PMID: 31568401 (Publication Type: Journal Article)

Chemical References

• NOB1 protein, human
• Nuclear Proteins
• PNO1 protein, human
• RNA, Small Interfering
• RNA-Binding Proteins
• Cyclooxygenase 2
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• Celecoxib

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (metabolism)
• Celecoxib (metabolism, pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cyclooxygenase 2 (metabolism)
• Humans
• Liver Neoplasms (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nuclear Proteins
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Small Interfering (pharmacology)
• RNA-Binding Proteins (genetics, metabolism)
• Signal Transduction (drug effects)
• Xenograft Model Antitumor Assays (methods)