Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer Journal Article
| Authors: | Altorki, N. K.; Port, J. L.; Zhang, F.; Golijanin, D.; Thaler, H. T.; Duffield-Lillico, A. J.; Subbaramaiah, K.; Dannenberg, A. J. |
| Article Title: | Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer |
| Abstract: | Purpose: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with non-small cell lung cancer (NSCLC). Experimental Design: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE2 in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17). Results: Levels of intratumoral PGE2 were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P < 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P < 0.001). Amounts of intratumoral COX-2 were ∼ 3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P < 0.0001) or without celecoxib (P < 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE2 were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (=0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98). Conclusions: Treatment with chemotherapy led to increased amounts of COX-2 and PGE 2 in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE2 but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy. © 2005 American Association for Cancer Research. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; protein expression; treatment outcome; aged; aged, 80 and over; middle aged; cancer combination chemotherapy; drug targeting; paclitaxel; preoperative care; combined modality therapy; carboplatin; lung non small cell cancer; lung resection; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; membrane proteins; blotting, western; correlation analysis; statistical significance; celecoxib; cyclooxygenase 2 inhibitor; cyclooxygenase 2 inhibitors; pyrazoles; sulfonamides; cyclooxygenase 2; prostaglandin e2; taxoids; taxane derivative; dinoprostone; bridged compounds; prostaglandin-endoperoxide synthases; cyclooxygenase inhibitors |
| Journal Title: | Clinical Cancer Research |
| Volume: | 11 |
| Issue: | 11 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-06-01 |
| Start Page: | 4191 |
| End Page: | 4197 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-05-0108 |
| PUBMED: | 15930356 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 35" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus" |
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