Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Pancreas. 2011 Apr;40(3):453-9. doi: 10.1097/MPA.0b013e31820b9733.
Targeting the cyclooxygenase-2 (COX-2)/prostanoid pathway is considered an intriguing approach for therapy and prevention of several cancers. However, the molecular mechanisms that underlie the protumorigenic properties of COX-2 in pancreatic cancer (PaCa) are still poorly understood. The purpose of the present study was to characterize the phenotype of COX-2 expressing syngeneic PaCa cells.
Cyclooxygenase-2-negative MIA PaCa-2 cells were stably transduced with COX-2 or control viruses (MP2 and MP2). Prostaglandin E2 (PGE2) production was measured by liquid chromatography and tandem mass spectrometry. Anchorage-dependent and -independent cell growth was analyzed by cell count and 3-dimensional collagen cell culture system, respectively. Changes in apoptotic gene expression were measured by a polymerase chain reaction array. The growth of tumors in vivo was evaluated in a xenograft animal model.
Stable expression of COX-2 increased anchorage-dependent and -independent cell growth, which was accompanied by elevated PGE2 production. Several significant differences in apoptotic gene expression were detected between MP2 and MP2 cells. Furthermore, MP2 cells grew faster than MP2 cells in a xenograft animal model.
Our results will provide the basis for more mechanistic studies on the role of COX-2 in PaCa and may help to develop novel therapeutic strategies aiming at the COX-2/prostanoid pathway.
靶向环氧化酶-2（COX-2）/前列腺素途径被认为是治疗和预防多种癌症的一种有吸引力的方法。然而，COX-2 在胰腺癌（PaCa）中促进肿瘤发生的分子机制仍知之甚少。本研究的目的是表征 COX-2 表达的同源 PaCa 细胞的表型。
用 COX-2 或对照病毒（MP2 和 MP2）稳定转染 COX-2 阴性的 MIA PaCa-2 细胞。通过液相色谱和串联质谱法测量前列腺素 E2（PGE2）的产生。通过细胞计数和 3 维胶原细胞培养系统分别分析锚定依赖性和非依赖性细胞生长。通过聚合酶链反应阵列测量凋亡基因表达的变化。在异种移植动物模型中评估体内肿瘤的生长。
COX-2 的稳定表达增加了锚定依赖性和非依赖性细胞生长，这伴随着 PGE2 产生的增加。在 MP2 和 MP2 细胞之间检测到凋亡基因表达的几个显著差异。此外，MP2 细胞在异种移植动物模型中的生长速度快于 MP2 细胞。
我们的结果将为 COX-2 在 PaCa 中的作用的更机制研究提供基础，并可能有助于开发针对 COX-2/前列腺素途径的新的治疗策略。
