Tuberc Respir Dis.  2009 Oct;67(4):303-310.

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

• Lee KH
• Yang SC

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-1beta, 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-1beta, 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.

Keyword

Cyclooxygenase 2; Polo-like kinase 1; Lung neoplasms

MeSH Terms

Carcinoma, Non-Small-Cell Lung
Cell Cycle
Cell Cycle Proteins
Cell Death
Cell Survival
Cyclooxygenase 2
Dinoprostone
Humans
Liver
Lung
Lung Neoplasms
Prostate
Protein-Serine-Threonine Kinases
Proteins
Proto-Oncogene Proteins
RNA, Small Interfering
Cell Cycle Proteins
Cyclooxygenase 2
Dinoprostone
Protein-Serine-Threonine Kinases
Proteins
Proto-Oncogene Proteins
RNA, Small Interfering

Figure

• 

  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.

• 

  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.

• 

  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.

• 

  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.

• 

  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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