SC58125 modulates TNF-?-induced HT-29 cells apoptosis through inhibiting I?B? degradation
- VernacularTitle:SC58125抑制I?B?降解调节TNF-?诱导的HT29细胞凋亡
- Author:
Xianda REN
;
Zhenghong TANG
;
Haiwei ZHANG
;
Chunling YE
;
Shaohui CAI
;
Kaihe YE
- Publication Type:Journal Article
- Keywords:
non-steroidal anti-inflammatory drugs;
tumor necrosis factor;
colorectal cancer;
apoptosis
- From:
Chinese Pharmacological Bulletin
2003;0(07):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate whether SC58125 synergized with TNF-? to induce HT-29 cell apoptosis and study the possible molecular mechanism. Methods By using MTT, agarose gel electrophoresis and flow cytometry, we examined the effect of SC58125/TNF-? on cell proliferation and apoptosis in HT-29 cells. The activity of caspase-3 and the changes of I?B? and NF-?B were also measured after treatment with SC58125 by Electrophoretic mobility shift assay and Western blot. Results Both SC58125 and TNF-? exhibited cytotoxicity, the combination of the two agents significantly reduced HT-29 cell viability in a dose-dependent manner. TNF-?-treated cells showed oligonucleosomal cleavage of genomic DNA. SC58125 significantly enhanced the inhibition of cell proliferation and inducement of cell apoptosis of TNF-?,the apoptotic index was increased from 11.2%?1.1% to 53.9%?2.1%. SC58125/TNF-?-induced apoptosis of HT-29 cells was accompanied by the induction of caspases-3. I?B? levels were substantially decreased after treatment with TNF-? and the degradation of I?B? was almost completely inhibited when SC58125 was added in NF-?B was activated in HT-29 cells after treatment with TNF-?, whereas pretreatment of HT-29 cells with SC58125 for 2 h, TNF-?-induced NF-?B DNA binding was profoundly inhibited. Conclusion SC58125 synergizes with TNF-? to inhibit cell growth and induce apoptosis in HT-29 cells, which may be mediated by activating caspases and preventing degradation of I?B?.
