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Published on: March 10, 2015
Targeting cyclooxygenase-2 with sodium butyrate and NSAIDs on colorectal adenoma/carcinoma cells
Zhi-Hong Zhang1, Qin Ouyang, Hua-Tian Gan
1Department of Gastroenterology, First Hospital, Western China University of Medical Sciences, Chengdu 610041, Sichuan Province, China. zhang-821@21cn.com
Aim:
The protective effects of sodium butyrate and NSAIDs (especially the highly selective COX-2 inhibitors) have attracted considerable interest recently. In this study, primary adenoma cells and HT-29 were used to investigate whether the above drugs would be effective for reducing proliferation and inducing apoptosis. Additionally, it was investigated whether NSAIDs would strengthen the effects of sodium butyrate and its possible mechanisms.
Methods:
In vitro primary cell culture of colorectal adenomas and HT-29 were used for this investigation. PGE2 isolated from HT-29 cell culture supernatants was investigated by ELISA. MTT was employed to detect the anti-proliferative effects on both adenoma and HT-29 culture cells. FCM was used for apoptosis rate and cell cycle analysis. The morphology of apoptotic cells was investigated by means of electromicroscopy.
Results:
Sodium butyrate could stimulate the secretion of PGE2, while NSAIDs inhibited it to below 30 pg/10(6) cells. Both butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis. The effects were time- and dose-dependent (P<0.05). Aspirin and NS-398 could enhance the effects of sodium butyrate. The effects were stronger while sodium butyrate was used in combination with NS-398 than it was used in combination with aspirin.
Conclusion:
Butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis respectively. NSAIDs could enhance the effects of sodium butyrate by down-regulating COX-2 expression. Selective COX-2 inhibitor is better than traditional NSAIDs.
Insights
Sodium butyrate and NSAIDs inhibit colorectal cancer cell proliferation and induce apoptosis. NSAIDs enhance butyrate's effects by down-regulating COX-2, with selective COX-2 inhibitors showing superior efficacy.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pharmacology
Background:
- Sodium butyrate and non-steroidal anti-inflammatory drugs (NSAIDs) show potential in cancer chemoprevention.
- NSAIDs, particularly selective COX-2 inhibitors, are of significant interest for their anti-cancer properties.
Purpose of the Study:
- To investigate the effects of sodium butyrate and NSAIDs on colorectal adenoma cell proliferation and apoptosis.
- To determine if NSAIDs enhance sodium butyrate's effects and elucidate the underlying mechanisms.
Main Methods:
- In vitro studies using primary colorectal adenoma cells and HT-29 cell line.
- ELISA for PGE2 quantification, MTT assay for proliferation, FCM for apoptosis and cell cycle analysis, and electromicroscopy for cell morphology.
- Investigated the impact of sodium butyrate and various NSAIDs, including selective COX-2 inhibitors.
Main Results:
- Sodium butyrate stimulated PGE2 secretion, while NSAIDs inhibited it.
- Both agents demonstrated dose- and time-dependent inhibition of cell proliferation and induction of apoptosis.
- NSAIDs, especially NS-398, potentiated the anti-proliferative and pro-apoptotic effects of sodium butyrate.
Conclusions:
- Sodium butyrate and NSAIDs effectively inhibit colorectal cancer cell proliferation and induce apoptosis.
- NSAIDs enhance sodium butyrate's efficacy through COX-2 down-regulation.
- Selective COX-2 inhibitors offer greater therapeutic potential compared to traditional NSAIDs.
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