Inhibition of Cyclooxygenase-2 Suppresses Angiogenesis and the Growth of Prostate Cancer in Vivo

Liu, Xin Hua; Kirschenbaum, Alexander; Shen, Yao; Lee, Richard; Holland, James F.; Levine, Alice C.

doi:10.1016/s0022-5347(05)67321-1

Cited by 315 publications

(168 citation statements)

References 23 publications

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“…COX-2 is also implicated in angiogenesis; COX-2 overexpression induces the production of vascular endothelial growth factor (VEGF), suggesting that COX-2 promotes progression, in part, by inducing angiogenesis. NS398 inhibits VEGF production and decreases angiogenesis in PC-3 prostate cancer cells (Liu et al, 2000). These observations may explain the stronger negative associations between aspirin use and advanced prostate cancer seen in this review.…”

Section: Discussionmentioning

confidence: 58%

Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis

2004

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Animal and laboratory studies suggest that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce prostate cancer risk. To assess this association, we conducted a systematic review and meta-analysis of observational studies published before January 2003. We derived summary odds ratios (ORs) using both fixed and random effects models and performed subgroup analyses to explore the possible sources of heterogeneity between combined studies. We identified 12 reports (five retrospective and seven prospective studies). Most studies of aspirin use reported inverse associations, but only two were statistically significant. The summary OR for the association between aspirin use and prostate cancer was 0.9 (95% confidence interval: 0.82 -0.99; test of homogeneity P ¼ 0.32), and varied from 1.0 for retrospective studies to 0.85 for prospective studies. Studies that measured exposure to a mixture of NSAIDs were less consistent. These results indicate an inverse association between aspirin use and prostate cancer risk. The current epidemiological evidence and, in particular, the strong and consistent laboratory evidence underline the need for additional epidemiological studies to confirm the direction and magnitude of the association.

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Section: Discussionmentioning

confidence: 58%

Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis

2004

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“…COX-2 expression has been reported in prostate cancer tissue. [24][25][26][27] However, there are some exceptions to this observation. Zha et al 30 reported that COX-2 is not consistently overexpressed in prostate cancer and found that proinflammatory atrophic lesions in prostate, which are said to be precursors of prostate cancer, express COX-2.…”

Section: Discussionmentioning

confidence: 98%

“…[20][21][22] Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme that converts arachidonic acid to prostaglandins. 23 A variety of mechanisms have been proposed to explain how COX-2 upregulation affects carcinogenesis, that is, by promoting angiogenesis, 24 by enhancing cellular motility 25 and by increasing cancer cell resistance to apoptosis. 26 Usually, COX-2 expression is either weak or absent in normal prostate tissue and overexpressed in prostate cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

Lorenzo

Placido

Autorino

et al. 2005

Prostate Cancer Prostatic Dis

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Objectives: To determine whether COX-2, bcl-2 and neoangiogenesis are related to human prostate cancer relapse after definitive surgical treatment and progression toward androgen independence and to evaluate the association between the patterns of these tumoral biomarkers and other standard clinico-pathological parameters (such as Gleason score, PSA, TNM stage). Materials and Methods: We retrospectively analyzed the records on 126 prostate cancer samples from patients treated at our University Hospital from 1995 to 2002. The 72 patients with clinically localized disease (group 1) had undergone radical prostatectomy. Another 54 patients (group 2) had metastatic androgen-independent disease. Archived material relating to the subjects was then immunostained for bcl-2, COX-2 and CD-31, using an anti-bcl-2 monoclonal primary antibody, an anti-COX-2 polyclonal rabbit antibody and an anti-CD-31 monoclonal mouse antibody to evaluate neoangiogenesis (MVD, microvessel density). Results: We found that bcl-2, COX-2 and MVD expression increased from group 1 to group 2. The intergroup difference was significant only for high MVD (Po0.05). On the other hand, high MVD, high bcl-2 and high COX-2 expression was correlated with a higher PSA level (Po0.01), whereas only a high MVD was also related with Gleason score (Po0.05). We used univariate analysis to evaluate the prognostic impact of biologic and clinico-pathologic parameters on the diseasefree-survival of 72 patients treated by radical prostatectomy. A total of 30 patients (41.6%) experienced biochemical relapse; bcl-2, COX-2 and MVD significantly correlated with disease relapse in these patients. In fact, we observed disease relapse in 24/45 (53%) with high bcl-2 expression, in 15/21 (71%) with a high MVD count and finally, in 30/58 (52%) with high COX-2 expression. Finally, PSA value and Gleason score were the only two biologic markers significantly associated to disease relapse in a multivariate analysis. Conclusions: Our results strongly support a role for bcl-2, COX-2 and angiogenesis in the development and progression of prostate cancer. Of course, we are aware of the small sample size considered in our study. Further investigations would better clarify the prognostic and therapeutic implications of these findings.

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“…The inducible form of COX, COX-2, is not detectable in most normal tissues, but is found highly expressed in malignant tumors of several histotypes (Kargman et al, 1995;Sano et al, 1995;Ristimaki et al, 1997;Deininger et al, 1999). The overexpression of COX-2 inhibits intercellular adhesion, susceptibility to apoptosis (Tsujii and DuBois, 1995), and increases the angiogenic and invasive potential of neoplastic cells (Tsujii et al, 1997(Tsujii et al, , 1998Liu et al, 2000). These cellular phenotypes are associated with an increased tumorigenic potential, indicating an important role of the COX pathway in the biology of neoplasms.…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor p53 inhibits transcriptional activation of invasion gene thromboxane synthase mediated by the proto-oncogenic factor ets-1

et al. 2003

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Cancer formation and progression is a complex process determined by several mechanisms that promote cell growth, invasiveness, neo-angiogenesis, and render neoplastic cells resistant to apoptosis. The tumor suppressor p53 and the proto-oncogenic factor ets-1 are important regulators of such mechanisms. While it is well established that p53 and ets-1 influence various aspects of cell behavior by regulating the transcription of specific genes, little is known about the functional relationship between these transcription factors. We found that the gene encoding thromboxane synthase (TXSA), which we recently identified as a factor promoting invasion and resistance to apoptosis in gliomas, is a novel target gene for both p53 and ets-1. We demonstrate that p53 and ets-1 coregulate TXSA in an antagonistic and interrelated manner, with ets-1 being a potent transcriptional activator and p53 inhibiting ets-1-dependent transcription. Negative interference with ets-1 transcription requires functional p53 and is lost in mutant p53 proteins. We show that ets-1 and p53 associate physically in vitro and in vivo and that their interaction, rather than a direct binding of p53 to the TXSA promoter, is required for transcriptional repression of TXSA by wild-type p53. An important implication of our findings is that the loss of p53-mediated negative control over ets-1-dependent transcription may lead to the acquisition of an invasive phenotype in tumor cells.

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Inhibition of Cyclooxygenase-2 Suppresses Angiogenesis and the Growth of Prostate Cancer in Vivo

Cited by 315 publications

References 23 publications

Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis

Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

Tumor suppressor p53 inhibits transcriptional activation of invasion gene thromboxane synthase mediated by the proto-oncogenic factor ets-1

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