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Synergistic tumoricidal effect between celecoxib and adenoviral-mediated delivery of mda-7 in human breast cancer cells.
Surgery. 2005 Sep; 138(3):422-30.S

Abstract

BACKGROUND

Celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, blocks growth and promotes apoptosis in breast cancer cells. The PI3K/Akt pathway is important in cell survival, and COX-2 and Akt might promote growth via a positive feedback loop. We have shown that adenoviral delivery of mda-7 (Ad-mda7) in breast cancer down-regulates Akt. We hypothesized that combining Ad-mda7 and celecoxib could mediate tumor suppression in COX-2 overexpressing breast cancer cells.

METHODS

Two COX-2 overexpressing human breast cancer cell lines (Her-18 and MDA-MB-436) were treated with celecoxib (20 micromol/L and 50 micromol/L) and Ad-mda7 (multiplicity of infection, 1000 and 2000 viral particles/cell). Adenovirus encoding the luciferase gene was used as a control. We assessed proliferation, cell cycle, apoptosis, prostaglandin E2 production, and changes in protein expression. Statistical analysis was performed by using the Student t test.

RESULTS

Regardless of HER-2/neu status, cell growth was markedly inhibited by celecoxib, Ad-mda7, and the combination compared with controls. Celecoxib + Ad-mda7 showed a greater than additive increase in cell death compared with either monotherapy (P < .05) and resulted in cell cycle block and apoptosis (P < .05). Both cell lines showed decreased prostaglandin E2 production after combination treatment compared with controls (P < .05), with decreased expression of COX-2, Akt, and phosphorylated Akt (P < .05).

CONCLUSIONS

Enhanced antitumor activity is achieved in breast cancer by combining celecoxib and Ad-mda7 regardless of HER-2/neu status. This occurs through inhibition of COX-2 expression and down-regulation of Akt. Combining Ad-mda7 with COX-2 inhibition provides a novel method of treatment in breast cancer.

Authors+Show Affiliations

Department of Surgical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16213894

Citation

Suh, Young-Jin, et al. "Synergistic Tumoricidal Effect Between Celecoxib and Adenoviral-mediated Delivery of Mda-7 in Human Breast Cancer Cells." Surgery, vol. 138, no. 3, 2005, pp. 422-30.
Suh YJ, Chada S, McKenzie T, et al. Synergistic tumoricidal effect between celecoxib and adenoviral-mediated delivery of mda-7 in human breast cancer cells. Surgery. 2005;138(3):422-30.
Suh, Y. J., Chada, S., McKenzie, T., Liu, Y., Swisher, S. G., Lucci, A., & Hunt, K. K. (2005). Synergistic tumoricidal effect between celecoxib and adenoviral-mediated delivery of mda-7 in human breast cancer cells. Surgery, 138(3), 422-30.
Suh YJ, et al. Synergistic Tumoricidal Effect Between Celecoxib and Adenoviral-mediated Delivery of Mda-7 in Human Breast Cancer Cells. Surgery. 2005;138(3):422-30. PubMed PMID: 16213894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic tumoricidal effect between celecoxib and adenoviral-mediated delivery of mda-7 in human breast cancer cells. AU - Suh,Young-Jin, AU - Chada,Sunil, AU - McKenzie,Tamra, AU - Liu,Yanna, AU - Swisher,Stephen G, AU - Lucci,Anthony, AU - Hunt,Kelly K, PY - 2005/01/24/received PY - 2005/06/13/revised PY - 2005/06/16/accepted PY - 2005/10/11/pubmed PY - 2005/11/16/medline PY - 2005/10/11/entrez SP - 422 EP - 30 JF - Surgery JO - Surgery VL - 138 IS - 3 N2 - BACKGROUND: Celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, blocks growth and promotes apoptosis in breast cancer cells. The PI3K/Akt pathway is important in cell survival, and COX-2 and Akt might promote growth via a positive feedback loop. We have shown that adenoviral delivery of mda-7 (Ad-mda7) in breast cancer down-regulates Akt. We hypothesized that combining Ad-mda7 and celecoxib could mediate tumor suppression in COX-2 overexpressing breast cancer cells. METHODS: Two COX-2 overexpressing human breast cancer cell lines (Her-18 and MDA-MB-436) were treated with celecoxib (20 micromol/L and 50 micromol/L) and Ad-mda7 (multiplicity of infection, 1000 and 2000 viral particles/cell). Adenovirus encoding the luciferase gene was used as a control. We assessed proliferation, cell cycle, apoptosis, prostaglandin E2 production, and changes in protein expression. Statistical analysis was performed by using the Student t test. RESULTS: Regardless of HER-2/neu status, cell growth was markedly inhibited by celecoxib, Ad-mda7, and the combination compared with controls. Celecoxib + Ad-mda7 showed a greater than additive increase in cell death compared with either monotherapy (P < .05) and resulted in cell cycle block and apoptosis (P < .05). Both cell lines showed decreased prostaglandin E2 production after combination treatment compared with controls (P < .05), with decreased expression of COX-2, Akt, and phosphorylated Akt (P < .05). CONCLUSIONS: Enhanced antitumor activity is achieved in breast cancer by combining celecoxib and Ad-mda7 regardless of HER-2/neu status. This occurs through inhibition of COX-2 expression and down-regulation of Akt. Combining Ad-mda7 with COX-2 inhibition provides a novel method of treatment in breast cancer. SN - 0039-6060 UR - https://www.unboundmedicine.com/medline/citation/16213894/Synergistic_tumoricidal_effect_between_celecoxib_and_adenoviral_mediated_delivery_of_mda_7_in_human_breast_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-6060(05)00366-1 DB - PRIME DP - Unbound Medicine ER -