COX-2 silencing inhibits cell proliferation in A549 cell

The Chinese-German Journal of Clinical Oncology 01/2011; 10(7):423-427. DOI: 10.1007/s10330-011-0829-0

ABSTRACT ObjectiveThe aim of this study was to explore the effects on malignant proliferation of A549 cell by silencing cyclooxygenase (COX)-2.

MethodsIn the present study, we constructed three siRNA vectors producing small interference RNA. The siRNA vectors and the vacant
vectors were transfected into A549 cell with lipofectamine respectively and the transfected cell strains were constructed.
The change of COX-2 expression levels was examined by Western blot and RT-PCR. The effects on the proliferation of lung cancer
cells were studied by cell growth curve, clonogenic assay and xenograft assays.

ResultsThe siRNA expression vectors produced marked effects in A549 cell but the inhibited effects were different. The effect of
psi-10 was best and the mRNA and protein levels of COX-2 reduced 61.2% and 56.2% respectively in A549-si10 cell in contrast
to the control. The growth of A549 cell slowed and the colony formation rate reduced after silencing COX-2. In xenograft assays,
the growth speeds of tumor became slow and the numbers of tumor reduced after silencing COX-2.

ConclusionThe si10 target of COX-2 has the best silencing effect in A549 cell and the best inhibition effect on malignant proliferation
of A549 cell in vivo and in vitro.

Key wordscyclooxygenase (COX)-2–A549 cell–malignant proliferation

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It seems certain that COX-2 is related to tumor and some data suggested that COX-2 might have relation to tumor malignance and angiogenesis. In order to elucidate the relationship between COX-2 and tumor invasive and angiogenic ability, we transfected human transitional cell carcinoma (TCC) cell line, EJ, permanently with a COX-2 expression vector or the mock vector. The EJ-COX(2) cells, which overexpressed COX-2, acquired increased invasiveness and angiogenic ability by activation of VEGF, uPA, and MMP-2. Increased invasiveness and angiogenic ability were reversed by treatment with either selective COX-2 inhibitor, NS-398, or dual COX inhibitor, indomethacin. These results demonstrate that overexpression of COX-2 can lead to phenotypic changes that alter the metastatic and angiogenic potential of TCC cancer cells.
    Biochemical and Biophysical Research Communications 01/2003; 299(5):886-90. · 2.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non-small cell lung cancer (NSCLC). With these observations, we designed a phase II trial to evaluate the efficacy and safety of erlotinib plus celecoxib in advanced NSCLC. Previously treated stage IIIB/IV NSCLC patients were given celecoxib at 400 mg orally twice daily and erlotinib at 150 mg orally daily until disease progression. Planned accrual was 40 patients. Tissue was collected for epidermal growth factor receptor (EGFR) analysis and COX-2 immunohistochemistry. Twenty-six patients were enrolled (17 men, 9 women; median age, 66 years). Eighteen and 21 patients had tissue available for EGFR analysis and COX-2 immunohistochemistry, respectively. The median progression-free survival (PFS) and overall survival were 2.0 and 9.2 months, respectively. Eleven of 21 patients tested had increased tumor COX-2 expression, which was strongly associated with prolonged PFS (P=0.048). Four patients on anticoagulation or with a history of peptic ulcer disease had grade 3/grade 4 upper gastrointestinal bleeding (GIB), prompting early study closure. Three patients with GIB had endoscopy that found peptic ulcers. The combination of erlotinib and celecoxib does not seem superior to erlotinib alone in unselected patients. However, longer PFS with high-tumor COX-2 expression suggests that trials of EGFR and COX-2 inhibitors may be warranted in this patient subset. GIB observed in our trial supports excluding patients with a history of peptic ulcer disease or those requiring therapeutic anticoagulation from future EGFR and COX-2 inhibitor studies.
    Clinical Cancer Research 05/2008; 14(7):2088-94. · 7.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aberrant or increased expression of cyclooxygenase (COX)-2 has been implicated in the pathogenesis of many diseases including carcinogenesis. COX-2 has been shown to be over-expressed in some human cancers. Employing semi-quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry we assessed COX-2 expression in samples of pair-matched benign and cancer tissue obtained from the same prostate cancer patient. Mean levels of COX-2 mRNA were 3.4-fold higher in prostate cancer tissue (n = 12) compared with the paired benign tissue. The immunoblot analysis demonstrated that as compared to benign tissue COX-2 protein was over-expressed in 10 of 12 samples examined. Immunohistochemical analysis also verified COX-2 over-expression in cancer than in benign tissue. To our knowledge, this is the first in vivo study showing an over-expression of COX-2 in prostate cancer. These data suggest that COX-2 inhibitors may be useful for prevention or therapy of prostate cancer in humans.
    The Prostate 02/2000; 42(1):73-8. · 3.84 Impact Factor