Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating peroxisome proliferator-activated receptor gamma.
OBJECTIVE
To examine whether and how rosiglitazone enhances apoptosis induced by fluorouracil in human colon cancer (HT-29) cells.


METHODS
Human colon cancer HT-29 cells were cultured in vitro and treated with fluorouracil and/or rosiglitazone. Proliferation and growth of HT-29 cells were evaluated by MTT assay and trypan blue exclusion methods, respectively. The apoptosis of HT-29 cells was determined by acridine orange/ethidium bromide staining and flow cytometry using PI fluorescence staining. The expressions of peroxisome proliferator-activated receptor gamma (PPARgamma), Bcl-2 and Bax in HT-29 cells were analyzed by Western blot.


RESULTS
Although rosiglitazone at the concentration below 30 micromol/L for 72 h exerted almost no inhibitory effect on proliferation and growth of HT-29 cells, it could significantly enhance fluorouracil-induced HT-29 cell proliferation and growth inhibition. Furthermore, 10 micromol/L rosilitazone did not induce apoptosis of HT-29 cells but dramatically enhanced fluorouracil-induced apoptosis of HT-29 cells. However, rosiglitazone did not improve apoptosis induced by fluorouracil in HT-29 cells pretreated with GW9662, a PPARgamma antagonist. Meanwhile, the expression of Bax and PPARgamma was up-regulated, while the expression of Bcl-2 was down regulated in HT-29 cells treated with rosiglitazone in a time-dependent manner. However, the effect of rosiglitazone on Bcl-2 and Bax was blocked or diminished in the presence of GW9662.


CONCLUSIONS
Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating PPARgamma.
Zhang
Yan-Qin
YQ
Cancer Research Institute of Nanhua University, Hengyang 421001, Hunan Province, China.
Tang
Xiao-Qing
XQ
Sun
Li
L
Dong
Lin
L
Qin
Yong
Y
Liu
Hua-Qing
HQ
Xia
Hong
H
Cao
Jian-Guo
JG
D000813:Anilides / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D005472:Fluorouracil / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000502:physiology
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; D051028:bcl-2-Associated X Protein; D000077154:Rosiglitazone; D005472:Fluorouracil