[Preventive effects of berberine on experimental colon cancer and relationship with cyclooxygenase-2 expression].
OBJECTIVE
To investigate the anti-colon cancer effects of berberine and possible relationship with cyclooxygenase-2.


METHODS
Wistar rat colon cancer model was induced by 1-2 dimethylhydrazine (DMH) (40 mg x kg(-1), sc) + 1% dextran sodium sulfate solution (DSS) (freely drinking). All rats were randomly divided into 3 groups: Control (DMH + DSS + solvant), meloxicam (Mel) (DMH + DSS + Mel 1.35 mg x kg(-1)), berberine (Ber) (DMH + DSS + Ber 100 mg x kg(-1)). The drugs were given orally once a day for 5 day per week. The body weight, the number of colon ACFs, the incidence and number of colon cancer in rats, as well as the morphological changes of rat colon tissues were evaluated. Human colon cancer lovo cell line was treated by either Ber or Mel in various concentrations (1 10(-6) mol x L(-1), 1 x 10(-5) mol x L(-1), 1 x 10(-4) mol x L(-1), 1 x 10(-3) mol x L(-1)) for 6, 12 and 24 h, respectively, and the cell growth was assayed by MTT method. RT-PCR and western-blot were used to evaluate the mRNA and protein expressions of COX-2 from lovo cells treated with Ber and Mel.


RESULTS
Ber significantly improved the dyscrasia induced by DMH + DSS, the both of body weight and general condition were better than control group. Ber also significantly inhibited ACF and colon cancer incidence in the rats treated by DMH + DSS for 10 weeks or 20 weeks, which was similar to that of Mel. Ber inhibited the proliferation of lovo cells in concentration- and time-dependent manners, and the IC50 values were significantly smaller than that of Mel at 6, 12 and 24 h after lovo cells were treated by either Ber or Mel. Ber also concentration-dependently decreased expressions of COX-2 mRNA and COX-2 protein from lovo cells.


CONCLUSIONS
Ber can inhibit ACF and tumor formation induced by DMH + DSS, and decrease the lovo cell proliferation index. The anti-tumor effects of Ber may involve in an unknown pathway through which the expressions of COX-2 mRNA and protein were inhibited.
Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China. wuke1997@yahoo.com.cn
Ke
K
Wu
Junxia
J
Yang
Qixin
Q
Zhou
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D058739:Aberrant Crypt Foci / Q000517:prevention & control; D000818:Animals; D001599:Berberine / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D001599:Berberine; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2; D019813:1,2-Dimethylhydrazine