【Abstract】Objective To investigate the relationship of expressions of cylooxygenase-2 (COX-2) and hypoxia-inducible factor-1α (HIF-1α) in hepatocelluar carcinoma (HCC) and the possible antineoplastic mechanism of selective COX-2 inhibitor.
Methods The expressions of COX-2 and HIF-1α in 53 cases of HCC tissues were detected immunohistochemically. Western blot was employed to evaluate the effects of variant concentration of COX-2 inhibitor meloxicam on expression of HIF-1α in Cobaltchloridestimulated SMMC-7721 cell.
ResultsOf 53 tumor tissues, the expression of COX-2 was 22/53 (41.5%) bly positive stained, 11/53 (20.8%) positive stained, and 20/53 (37.7%) negative stained. Meanwhile the expression of HIF-1α was 18/53 （34.0%） bly positive stained, 18/53 （34.0%）positive stained, 17/53（32.1%） negative stained. The expression of COX-2 was correlated positively with HIF-1α in HCC （r=0.440, P＜0.01）. The expression of HIF-1α increased sharply from 0.185±0.057 (no Cobaltchloride-stimulated) to 1.011±0.131 (Cobaltchloride-stimulated), and meloxicam could inhibit the expression of HIF-1α at either condition (P＜0.05).
ConclusionMeloxicam could inhibit the expression of HIF-1α in a concentration-dependent manner in the Cobaltchloridestimulated SMMC-7721 cell. The antineoplastic activity of selective COX-2 inhibitor was possibly, at least in part, mediated by HIF-1α.
Citation：
JIANG Chao,ZHANG Feng,WANG Shaojun,ZOU Qifei. Expressions of Cyclooxygenase-2 and Hypoxia-Inducible Factor-1α in Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2006, 13(2): 142-141. doi:
Copy
Copyright © the editorial department of CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY of West China Medical Publisher. All rights reserved
| 1. |
Huang SP, Wu MS, Shun CT, et al. Cyclooxygenase2 increases hypoxiainducible factor1 and vascular endothelial growth factor to promote angiogenesis in gastric carcinoma [Ｊ]. J Biomed Sci， 2005; 12(1)∶229.
|
| 2. |
Bae SH, Jung ES, Park YM, et al. Expression of cyclooxygenase2 (COX2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX2 inhibitor, NS398 [Ｊ]. Clin Cancer Res， 2001; 7(5)∶ 1410.
|
| 3. |
Fosslien E. Review: molecular pathology of cyclooxygenase2 in cancerinduced angiogenesis [Ｊ]. Ann Clin Lab Sci, 2001; 31(4)∶325.
|
| 4. |
Gallo O, Franchi A, Magnelli L, et al. Cyclooxygenase2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis [Ｊ]. Neoplasia, 2001; 3(1)∶53.
|
| 5. |
Leahy KM, Koki AT, Masferrer JL. Role of cyclooxygenases in angiogenesis [Ｊ]. Curr Med Chem， 2000; 7(11)∶1163.
|
| 6. |
Semenza GL. Targeting HIF1 for cancer therapy [Ｊ]. Nat Rev Cancer, 2003; 3(10)∶721.
|
| 7. |
丁磊， 陈孝平， 王海平. 肝癌和癌旁组织中HIF1α基因蛋白的表达及其临床意义 [Ｊ]. 肝胆外科杂志， 2004; 12(1)∶32.
|
| 8. |
Blancher C, Moore JW , Talks KL, et al. Relationship of hypoxiainducible factor (HIF)1alpha and HIF2alpha expression to vascular endothelial growth factor induction and hypoxia survival in human breast cancer cell lines [Ｊ]. Cancer Res， 2000; 60(24)∶710.
|
| 9. |
Xu XC. COX2 inhibitors in cancer treatment and prevention, a recent development [Ｊ]. Anticancer Drugs， 2002; 13(2)∶127.
|
| 10. |
Yao M, Kargman S, Lam EC, et al. Inhibition of cyclooxygenase2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice [Ｊ]. Cancer Research, 2003; 63(3)∶ 586.
|
| 11. |
Abiru S, Nakao K, Ichikawa T, et al. Aspirin and NS398 inhibit hepatocyte growth factorinduced invasiveness of human hepatoma cells [Ｊ]. Hepatology， 2002; 35(5)∶1117.
|
- 1. Huang SP, Wu MS, Shun CT, et al. Cyclooxygenase2 increases hypoxiainducible factor1 and vascular endothelial growth factor to promote angiogenesis in gastric carcinoma [Ｊ]. J Biomed Sci， 2005; 12(1)∶229.
- 2. Bae SH, Jung ES, Park YM, et al. Expression of cyclooxygenase2 (COX2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX2 inhibitor, NS398 [Ｊ]. Clin Cancer Res， 2001; 7(5)∶ 1410.
- 3. Fosslien E. Review: molecular pathology of cyclooxygenase2 in cancerinduced angiogenesis [Ｊ]. Ann Clin Lab Sci, 2001; 31(4)∶325.
- 4. Gallo O, Franchi A, Magnelli L, et al. Cyclooxygenase2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis [Ｊ]. Neoplasia, 2001; 3(1)∶53.
- 5. Leahy KM, Koki AT, Masferrer JL. Role of cyclooxygenases in angiogenesis [Ｊ]. Curr Med Chem， 2000; 7(11)∶1163.
- 6. Semenza GL. Targeting HIF1 for cancer therapy [Ｊ]. Nat Rev Cancer, 2003; 3(10)∶721.
- 7. 丁磊， 陈孝平， 王海平. 肝癌和癌旁组织中HIF1α基因蛋白的表达及其临床意义 [Ｊ]. 肝胆外科杂志， 2004; 12(1)∶32.
- 8. Blancher C, Moore JW , Talks KL, et al. Relationship of hypoxiainducible factor (HIF)1alpha and HIF2alpha expression to vascular endothelial growth factor induction and hypoxia survival in human breast cancer cell lines [Ｊ]. Cancer Res， 2000; 60(24)∶710.
- 9. Xu XC. COX2 inhibitors in cancer treatment and prevention, a recent development [Ｊ]. Anticancer Drugs， 2002; 13(2)∶127.
- 10. Yao M, Kargman S, Lam EC, et al. Inhibition of cyclooxygenase2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice [Ｊ]. Cancer Research, 2003; 63(3)∶ 586.
- 11. Abiru S, Nakao K, Ichikawa T, et al. Aspirin and NS398 inhibit hepatocyte growth factorinduced invasiveness of human hepatoma cells [Ｊ]. Hepatology， 2002; 35(5)∶1117.
