Antitumor activity of the selective cyclooxygenase-2 inhibitor, celecoxib, on breast cancer in Vitro and in Vivo

Abstract

BackgroundCyclooxygenase-2(COX-2) promotes carcinogenesis, tumor proliferation, angiogenesis, prevention of apoptosis, and immunosuppression. Meanwhile, COX-2 over-expression has been associated with tumor behavior and prognosis in several cancers. This study investigated the antitumor effects of the selective COX-2 inhibitor, Celecoxib, on breast cancer in vitro and in vivo.MethodsHuman breast cancer MCF-7 and MDA-MB-231 cells were cultured with different concentration (10, 20, 40 μmol/L) of celecoxib after 0-96 hours in vitro. MTT assay was used to determine the growth inhibition of breast cancer cells in vitro. The expression of COX-2 on mRNA was measured by real-time quantitive PCR analysis. Flow cytometry was performed to analyze the cell cycle of MCF-7 cells. Levels of PGE2 were measured by ELISA method. The in vivo therapeutic effects of celecoxib were determined using rat breast cancer chemically induced by 7,12-dimethylben anthracene (DMBA).ResultsThe inhibition of proliferation of both MCF-7 and MDA-MB-231 cells in vitro by celecoxib was observerd in time and dose dependent manner. Celecoxib effectively down-regulated the expression of COX-2. The cell cycle was arrested at G0/G1, and rate of cells in S phase was obviously decreased. Levels of PGE2 were inhibited by Celecoxib. The tumor incidence rate of the celecoxib group was lower than that of the control group. In addition, the tumor latency period of the celecoxib group was longer than that of the control group.ConclusionsCelecoxib inhibited the proliferation of breast cancer cell lines in vitro, and prevented the occurrence of rat breast cancer chemically induced by DMBA. Therefore, celecoxib exhibits an antitumor activity and seems to be effective in anti-tumor therapy.

Apoptotic Effects of Etodolac in Breast Cancer Cell Cultures

“…In prostate cancer cell lines, dose-response relation was found to be weaker for etodolac compared to NS-398, another selective COX-2 inhibitor [11]. Strange inding was that COX-2 expression did not necessarily correlated with its activity and etodolac was able to suppress PGE2 and tumour invasiveness without efecting protein COX-2 levels [14,39]. Similarly, COX-2 expression and apoptosis were examined in HT-29 colon cancer cell lines, and high expression of COX-2 was detected in HT-29 cells with mutant APC.…”

“…The most commonly used, FDA-approved, COX-2 inhibitor in market is celecoxib. A recent study presented full efects of celecoxib both in vivo and in vitro on breast cancer cells [39]. Growth inhibitory efects of celecoxib were clearly observable between ranges 10 and 40 μM, especially after 72-and 96-h incubations.…”

Calotropis gigantea Leaf Extract Increases the Efficacy of 5-Fluorouracil and Decreases the Efficacy of Doxorubicin in Widr Colon Cancer Cell Culture

“…These cells were successfully derived from HT-29 cells (Nurulita et al, 2011). The specifications of WiDr cells are, able to produce carcinoembryonic antigen and can finish one cell cycle in 15 hours (Dai et al, 2012). Doxorubicin and Fluorouracil 5 are selected chemotherapy agents that have been used more than three recent decades.…”

Celecoxib/PLGA Suprime Angiogénesis y Metástasis Pulmonar de un Cáncer Mamario Murino Experimental

“…COX-2 es capaz de promover carcinogénesis, proliferación tumoral, AG, la prevención de la apoptosis, y la inmunosupresión (Koki & Masferrer, 2002), además su sobreexpresión se ha relacionado con el comportamiento desfavorable del tumor y un mal pronóstico en varios tipos de cáncer (Dai et al, 2012;Hill et al, 2012;Shin et al, 2013).…”