Abstract 1474: Polo-like kinase-1 regulation by cyclooxygenase-2 in non small cell lung cancer
Authors: Lee Kyu Hwa , Lee Sang-Min , Yim Jae-Jun , Yoo Chul-Gyu , Lee Choon-Taek , Kim Young Whan , Han Sung Koo , Shim Young-Soo , Sharma Sherven , Dubinett Steven M. , Yang Seok-Chul 
Published: February 2011

Abstract
Background: Despite focused research in conventional therapies and considerable advances in the understanding of the molecular carcinogenesis of lung cancer, the 5-year survival rate for all lung cancer patients remains less than 15%. Because most lung cancer already invaded locally or systemically at the first diagnosis, the understanding of mechanism of this process is of importance. Elevated tumor cyclooxygenase-2 (COX-2) and enhanced production of prostaglandin E2 (PGE2) are associated with tumor invasion, metastasis, and poor prognosis in many solid tumors including non-small cell lung cancer (NSCLC). 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a catabolic enzyme for biological inactivation of PGE2. Knock down of 15-PGDH resulted in strong increase of PGE2 production and increased cell growth by 31% in anchorage-independent conditions. Polo-like kinase-1 (PLK-1) is a key player in the mitotic regulation of both normal and malignant transformed cells. 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 have a strong correlation in prostate carcinoma. But there are few studies about these two targets for cancer prevention and treatment. The goal of this study is to evaluate the possible association between COX-2 and PLK-1 in NSCLC.
Methods: In this study, we investigated the interaction and regulation of COX-2 and PLK-1 in human NSCLC cell lines including A549 (human lung adenocarcinoma) and NCI H157 (human squamous cell carcinoma). Expressions of COX-2 and PLK-1 were evaluated after COX-2 induction/inhibition or gene modified cell lines and PLK-1 siRNA treatment. The regulation of 15-PGDH was also assessed after 16,16-dimethyl-PGE2 stimulation or PLK-1 siRNA treatment in NSCLC.
Results: COX-2 induction by IL-1β reduced the expression of PLK-1 in A549 and NCI H157 cell lines. Western results of COX-2 and PLK-1 showed the reverse expression of these proteins in A549 COX-2 sense (COX-2-S) or anti-sense (COX-2-AS) cell lines and these proteins were binded with each other in immunoprecipitation assay. Knock out of PLK-1 expression by PLK-1 siRNA augmented COX-2 and 15-PGDH in NSCLC. Likewise, the treatment of PGE2 on a dose dependent manner in A549 cells resulted in the reduction of COX-2 and 15-PGDH expression.
Conclusions: These results demonstrate that COX-2 and PLK-1 directly interacts with each other, and possibly being regulated and inhibited by each other in protein levels in NSCLC but final product of COX-2, PGE2 is regulated differently; reduction of PLK-1 induces COX-2 and PGE2 degradation enzyme such as 15-PGDH, causing more degradation of COX-2 end products such as PGE2 even though more induction of COX-2. These findings suggest that these proteins may be one of potential interesting targets for new molecular therapies in NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1474.