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Lee and Yang: Relation between Cyclooxygenase-2 and Polo-like Kinase-1 in Non-Small Cell Lung Cancer
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2009; 67(4): 303-310.

Published online: 31 October 2009

DOI: https://doi.org/10.4046/trd.2009.67.4.303

Relation between Cyclooxygenase-2 and Polo-like Kinase-1 in Non-Small Cell Lung Cancer

Kyu-Hwa Lee, M.S., Seok-Chul Yang, M.D.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University, College of Medicine, Seoul, Korea.

Address for correspondence: Seok-Chul Yang, M.D. Division of Pulmonary and Critical Care Medine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul 110-744, Korea. Phone: 82-2-2072-0354, Fax: 82-2-762-9662, scyang@snu.ac.kr

Received 9 September 2009       Accepted 7 October 2009

Copyright©2009. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Background

Elevated expression of cyclooxygenase-2 (COX-2) and Polo-like kinase-1 (PLK-1) is observed in a wide variety of cancers. Augmented expression of COX-2 and enhanced production of prostaglandin E2 (PGE2) are associated with increased tumor cell survival and malignancy; COX-2 has been implicated in the control of human non-small cell lung carcinoma (NSCLC) cell growth. PLK-1 siRNA induced the cell death of lung cancer cells and the systemic administration of PLK-1 siRNA/atelocollagen complex inhibited the growth of lung cancer in a liver metastatic murine model. COX-2 and PLK-1 are involved in proliferation and in cell cycle regulation, and there is a significant correlation between their interaction in prostate carcinoma.

Methods

In this study, we investigated the pattern of COX-2 and PLK-1 expression in NSCLC, after treatment with IL-1β, COX-2 inhibitor and PLK-1 siRNA.

Results

Expression of PLK-1 was decreased in A549 COX-2 sense cells, and was increased in A549 COX-2 anti-sense cells. Knock out of PLK-1 expression by PLK-1 siRNA augmented COX-2 expression in A549 and NCl-H157 cells. When A549 and NCI-H157 cells were treated with COX-2 inhibitor on a dose-dependent basis, PLK-1 and COX-2 were reduced. However, when the expression of COX-2 was induced by IL-1β, the production of PLK-1 decreased.

Conclusion

These results demonstrate that COX-2 and PLK-1 are regulated and inhibited by each other in NSCLC, and suggest that these proteins have a reverse relationship in NSCLC.

Keywords: Cyclooxygenase 2, Polo-like kinase 1, Lung neoplasms

Figures and Tables

Figure 1
Expression of COX-2 and PLK-1 according to concentration of Interleukin (IL)-1β treatment. A549 (A) and NCI-H157 (B) cells were treated with 0, 0.015, 0.05, 0.1, 1, 1.5 ng/mL for 24 hours. Analysis of COX-2 and PLK-1 expression was done by Western blot. COX-2 protein expression was increased in dose dependent manner, but the expression of PLK-1 was decreased.
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Figure 2
Expression of COX-2 and PLK-1 according to concentration of Interleukin (IL)-1β treatment. A549 and NCI-H157 cells were treated with 0.1, 1 ng/mL respectively for 0, 1, 2, 4, 8, 16, 20, 24 hours. Analysis of COX-2 and PLK-1 expression was done by Western blot. (A) In A549 cells, the maximum level of COX-2 expression was detected at 4 hour of exposure to IL-1β, and the minimum level of PLK-1 expression was detected from 4 hour to 8 hour of exposure to IL-1β. (B) In NCI-H157 cells, the maximum level of COX-2 expression was detected at 24 hour of exposure to IL-1β, and the minimum level of PLK-1 expression was detected at 16 hour of exposure to IL-1β.
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Figure 3
Expression of COX-2 and PLK-1 according to concentration of celecoxib treatment. A549 (A) and NCI-H157 (B) cells were treated with 0, 10, 20, 30, 40, 50 µM (Land 1~6) for 24 hours. Analysis of COX-2 and PLK-1 expression was done by western blot. Expression of PLK-1, as well as COX-2, was decreased in dose dependent manner.
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Figure 4
Expression of COX-2 and PLK-1 in COX-2 gene modified human adenocarcinoma cell lines. According to the expression of COX-2 is increase, PLK-1 expression is decreased. A549-vector: A549 COX-2 vector only cell line; A549-S: A549 COX-2 sense cell line; A549-AS: A549 COX-2 anti-sense cell line.
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Figure 5
Expression of COX-2 after PLK-1 inhibition in non-small cell lung cancer. Transfection with PLK-1 siRNA and control siRNA (+: 50 nM; ++: 100 nM), to A549 cells (A) and NCI-H157 cells (B) activated COX-2 expression. si-cont: control siRNA; siPLK-1: PLK-1 siRNA.
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