BACKGROUND: Epidemiological studies have revealed a protective effect of NSAIDs, which principally target cyclooxygenase (COX)-1 and COX-2, on the development of colorectal cancer. Increased expression of COX-2 was shown in colorectal adenocarcinoma. However, some effects were shown to be COX-independent. Here, we compared two selective COX-2 inhibitors for their effect on the growth of colorectal tumour cells in vitro. MATERIALS AND METHODS: Fifteen tumour cell lines were characterized for COX-1 and COX-2 expression by Western blot and RT-PCR. The effect of celecoxib and rofecoxib on their growth was assessed by staining of DNA with crystal violet. RESULTS: COX-2 expression varied among cell lines, whereas COX-1 was always expressed. Rofecoxib displayed a limited dose-related effect on cell proliferation, whereas celecoxib strongly inhibited cell growth at high concentrations. Both effects appeared COX-2-independent. CONCLUSION: Rofecoxib, which is devoid of apoptotic effect at high concentration but efficient at pharmacological concentrations, revealed a potential new mechanism of action of NSAIDs towards colorectal cancer.
BACKGROUND: Epidemiological studies have revealed a protective effect of NSAIDs, which principally target cyclooxygenase (COX)-1 and COX-2, on the development of colorectal cancer. Increased expression of COX-2 was shown in colorectal adenocarcinoma. However, some effects were shown to be COX-independent. Here, we compared two selective COX-2 inhibitors for their effect on the growth of colorectal tumour cells in vitro. MATERIALS AND METHODS: Fifteen tumour cell lines were characterized for COX-1 and COX-2 expression by Western blot and RT-PCR. The effect of celecoxib and rofecoxib on their growth was assessed by staining of DNA with crystal violet. RESULTS:COX-2 expression varied among cell lines, whereas COX-1 was always expressed. Rofecoxib displayed a limited dose-related effect on cell proliferation, whereas celecoxib strongly inhibited cell growth at high concentrations. Both effects appeared COX-2-independent. CONCLUSION:Rofecoxib, which is devoid of apoptotic effect at high concentration but efficient at pharmacological concentrations, revealed a potential new mechanism of action of NSAIDs towards colorectal cancer.
Authors: Gabriela Uribe; Romain Villéger; Philippe Bressollier; Rachel N Dillard; Daniel L Worthley; Timothy C Wang; Don W Powell; Maria C Urdaci; Irina V Pinchuk Journal: Cell Microbiol Date: 2018-07-26 Impact factor: 3.715
Authors: Manisha Bajpai; Darren N Seril; James Van Gurp; Xin Geng; Janet Alvarez; Carlos D Minacapelli; Steve Gorin; Koushik K Das; Elizabeth Poplin; Jerry Cheng; Peter S Amenta; Kiron M Das Journal: Dig Dis Sci Date: 2018-11-26 Impact factor: 3.199