The Cyclooxygenase-2 Inhibitor Celecoxib Attenuates Hepatocellular Carcinoma Growth and c-Met Expression in an Orthotopic Mouse Model

Abstract

To demonstrate in vivo tumor growth inhibition, the liver cancer cell lines HepG2, BEL7402, and SMMC7721 were independently inoculated into the livers of 45 6-week-old nude mice. After 24 h, mice were randomly divided into celecoxib (intragastric celecoxib suspension, 300 mg/kg), negative control (equal volume intragastric saline), and positive control (intraperitoneal injection of 6 mg/kg doxorubicin) and treated once per day for 3 days. Body weights, tumor diameters, and tumor expressions of proliferating cell nuclear antigen (PCNA) and c-Met were determined at 23 days posttreatments. Significant increases in body weight were observed in celecoxib- or doxorubicin-treated mice compared to saline-treated animals and tumor growth was significantly attenuated, accompanied by downregulation of tumor PCNA expression (p < 0.01). Weight gain, attenuated tumor growth, and reduced PCNA expression were similar following celecoxib or doxorubicin treatment. Celecoxib also significantly reduced c-Met expression in HepG2- and BEL7402-induced tumors, but not SMMC7721-induced tumors (p < 0.05). In conclusion, celecoxib effectively suppressed the in vivo growth of liver cancer in an orthotopic tumor model. Celecoxib also inhibited tumor cell PCNA expression independent of changes in c-Met expression, with some variability between different implanted cell lines. This preclinical demonstration of celecoxib efficacy and safety provides a foundation for future clinical investigations involving use of this agent alone or as a component of chemotherapeutic regimens for treatment of HCC.

MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting cyclooxygenase-2

“…It has been demonstrated in vivo and in vitro that the expression of COX-2 is associated with the proliferation and metastasis of tumor cells (22). In addition, COX-2 has been proposed as a potential pharmacologic target to decrease the growth of certain human tumors (23). Previous studies identified that the expression of COX-2 was upregulated in GC and may be targeted by miR-143 (24,25), which suggests that targeted COX-2 by miRNA may serve as a novel approach for the treatment of GC.…”

Effects of silencing cyclooxygenase-2 expression via RNA interference on the tumorigenicity of the SMMC-7721 human hepatocarcinoma cell line

“…Existing literature indicates that a COX-2-specific inhibitor could suppress tumor growth both in vitro and in an HCC animal model. However, all these inhibitors have not yet been clinically applied (28,29). Researchers have found that COX-2 inhibitors could adversely affect cardiovascular and renal functions (30).…”

The effect of oleuropein from olive leaf (Olea europaea) extract on Ca2+ homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells

“…It has been shown that celecoxib, a selective inhibitor of COX-2, at the concentration of 20 mM, enhanced the cytotoxic effects of anti-cancer agents (doxorubicin, 5-fluorouracil, sorafenib or gefitinib) on HepG2 cells (Roy et al, 2010;Cui et al, 2014). Furthermore, celecoxib effectively suppressed the in vivo growth of liver cancer in an orthotopic tumor model (Yin et al, 2011). Therefore celecoxib was used in oleuropeintreated HepG2 cells.…”