Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammation, with notable benefits in increasing survival and reducing risk of several types of cancer; however, expert consensus is that the risks of harm from using these drugs long-term are greater than the benefits for prevention against cancer for many people.
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Modes of action: microenvironment effects
Mechanisms by which celecoxib may act on cancer prevention and treatment include apoptosis induction, anti-angiogenic effect, microenvironment regulation, proliferation inhibition, resensitization of antitumor drugs, and immunoregulation.1Li J, Hao Q, Cao W, Vadgama JV, Wu Y. Celecoxib in breast cancer prevention and therapy. Cancer Management and Research. 2018 Oct 26;10:4653-4667.
Celecoxib affected genes and pathways involved in inflammation and malignant transformation in tumors but not normal tissues.2Sagiv E, Sheffer M et al. Gene expression following exposure to celecoxib in humans: pathways of inflammation and carcinogenesis are activated in tumors but not normal tissues. Digestion. 2011;84(3):169-84.
Notable preclinical evidencetesting a drug, a procedure, or another medical treatment in isolated cells or in animals; preclinical evidence is considered only an initial indication of possible effects in people; clinical evidence is summarized in How can non-aspirin NSAIDs help me? What the research says ›
Improving treatment outcomes: preclinical evidence
Synergistic effects with conventional and complementary therapies
- Anticancer effects from a combination dose of celecoxib and fish oil in rats3Negi AK, Kansal S, Bhatnagar A, Agnihotri N. Alteration in apoptosis and cell cycle by celecoxib and/or fish oil in 7,12-dimethyl benzene (α) anthracene-induced mammary carcinogenesis. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine. 2013 Dec;34(6):3753-64.
- Anticancer effects in breast cancer, including sensitizing tumors to antitumor drugs4Li J, Hao Q, Cao W, Vadgama JV, Wu Y. Celecoxib in breast cancer prevention and therapy. Cancer Management and Research. 2018 Oct 26;10:4653-4667.
- Increased sensitivity of colon cancer cells to radiotherapy5Sada O, Ahmed K, Jeldo A, Shafi M. Role of anti-inflammatory drugs in the colorectal cancer. Hospital Pharmacy. 2020 Jun;55(3):168-180.
- Anticancer effects in melanoma when used with rapamycin6Bundscherer A, Hafner C et al. Antiproliferative and proapoptotic effects of rapamycin and celecoxib in malignant melanoma cell lines. Oncology Reports. 2008 Feb;19(2):547-53.
- Significantly enhanced effects of cisplatin on intrinsically resistant primary ovarian cancer cells when used in combination with sorafenib and sildenafil before chemotherapy, with more limited results for oxaliplatin and carboplatin7Webb T, Carter J et al. Celecoxib enhances [sorafenib + sildenafil] lethality in cancer cells and reverts platinum chemotherapy resistance. Cancer Biology & Therapy. 2015;16(11):1660-70.
- Synergistic effects with EGCG,8Härdtner C, Multhoff G, Falk W, Radons J. (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. European Journal of Pharmacology. 2012 Jun 5;684(1-3):36-43. curcumin,Lev-Ari S, Strier L et al. Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clinical Cancer Research. 2005 Sep 15;11(18):6738-44. or nintedanib9Mateus PAM, Kido LA, Silva RS, Cagnon VHA, Montico F. Association of anti-inflammatory and antiangiogenic therapies negatively influences prostate cancer progression in TRAMP mice. The Prostate. 2019 Apr;79(5):515-535.
- Increased sensitivity to doxorubicin in esophageal squamous cell carcinoma cells10Yu L, Wu WK, Li ZJ et al. Enhancement of doxorubicin cytotoxicity on human esophageal squamous cell carcinoma cells by indomethacin and 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC236) via inhibiting P-glycoprotein activity. Molecular Pharmacology. 2009 Jun;75(6):1364-73.
- Effective against taxane-resistant ovarian cancer with minimal neurotoxicity or immunosuppression in mice11Tomar V, Kukreti S, Prakash S, Madan J, Chandra R. Noscapine and its analogs as chemotherapeutic agent: current updates. Current Topics in Medicinal Chemistry. 2017;17(2):174-188.
- Inhibited proliferation of both paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells12Zhou J, Gupta K et al. Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine. Journal of Biological Chemistry. 2002 Oct 18;277(42):39777-85.
- Increased anticancer activity of cisplatin against drug-resistant ovarian cancer cells13Shen W, Liang B, Yin J, Li X, Cheng J. Noscapine increases the sensitivity of drug-resistant ovarian cancer cell line SKOV3/DDP to cisplatin by regulating cell cycle and activating apoptotic pathways. Cell Biochemistry and Biophysics. 2015 May;72(1):203-13; Su W1, Huang L et al. Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α. Cancer Letters. 2011 Jun 1;305(1):94-9.
Optimizing your body terrain: preclinical evidence
Blood sugar and insulin resistance
- Diclofenac down-regulated glucose metabolism in cell lines of leukemia, melanoma, and prostate cancer14Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016;10:610.
- Celecoxib regulated the immune system and the tumor microenvironment in cell studies for breast cancer15Li J, Hao Q, Cao W, Vadgama JV, Wu Y. Celecoxib in breast cancer prevention and therapy. Cancer Management and Research. 2018 Oct 26;10:4653-4667.
- Celecoxib decreased release of CXCL9 and CXCL10, chemokines associated with improved survival, in high-grade serous ovarian cancer cells16Bronger H, Singer J et al. CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer. British Journal of Cancer. 2016 Aug 23;115(5):553-63.
- Celecoxib reduced prostaglandin E2 and prevented the local and systemic expansion of all MDSC subtypes in animals17Veltman JD, Lambers ME et al. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer. 2010 Aug 30;10:464.
- Diclofenac modulated immune suppression in preclinical trials18Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016;10:610.
Managing side effects and promoting wellness: preclinical evidence
- Weight gain in late-stage cachetic mice with tumors of the colon or head and neck with celecoxib use in preclinical studies19Davis TW, Zweifel BS et al. Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. Journal of Pharmacology and Experimental Therapeutics. 2004 Mar;308(3):929-34.
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