[Correlation between Stat3 signal transduction pathway and expression of cyclooxygenase-2 in colorectal cancer cells].
OBJECTIVE
To explore the expression of Stat3 signal transduction pathway and expression of cyclooxygenase-2 (COX-2) in colorectal cancer cells and their correlation with the clinicopathological parameters of colorectal cancer, and to reveal the mechanism of Stat3 signal transduction pathway regulating the expression of cCOX-2 in colorectal cancer cells.


METHODS
RT-PCR was used to detect the mRNA expression of Stat3 and COX-2 and immunohistochemistry was used to detect the protein expression of Stat3 and COX-2 in 50 specimens excised during operation from 50 patients with colorectal cancer aged 58 (37-75). Human colorectal cancer cells of the HT-29 strain were cultured. MTT method was used to examine the growth of the cells. AG490, an inhibitor of the upstream kinase JAK2 of Stat3 was added in to the culture fluid. 24, 48, and 72 hours later flow cytometry was used to examine the apoptosis of the cells.


RESULTS
The mRNA expression levels of Stat3 and COX-2 in the colorectal cancer tissues were 1.97 and 1.88 times those of the adjacent normal tissues (both P < 0.05). The mRNA expression levels of Stat3 and COX-2 in the colorectal cancer tissues of the patients with lymph node metastasis were both significantly higher than those of the patients without lymph node metastasis (both P < 0.05). The mRNA expression levels of Stat3 and COX-2 in the colorectal cancer tissues of the patients of cancer with low differentiation were both significantly higher than those of the patients with high differentiation (both P < 0.05). Pearson correlation analysis showed that Stat3 mRNA expression was linearly correlated with COX-2 mRNA expression (r = 0.749, P < 0.01). The protein expression levels of Stat3 and COX-2 in the colorectal caner tissues were significantly higher than those in the adjacent normal tissues (both P < 0.01). AG490 time and dose-dependently inhibited the growth of the HKC cells, induced apoptosis of the HKC cells, and down-regulated the protein expression of Stas3 and COX-2.


CONCLUSIONS
Overexpression of Stat3 and COX-2 may play a critical role in the development of colorectal cancer. Stat3 pathway influences the proliferation and apoptosis of colorectal cells and COX-2 gene expression. Blockade of the Stat3 signal pathway inhibits the proliferation and promotes the apoptosis of colorectal cancer cells.
Zhang
Hui
H
Department II of Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, China.
Wang
Shan
S
Zhang
You-cheng
YC
Ye
Ying-jiang
YJ
Cui
Zhi-rong
ZR
Fang
Wei-gang
WG
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D051546:Cyclooxygenase 2