Non-aspirin Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

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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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

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.

Preclinical evidence 

Notable preclinical evidence is presented here; clinical evidence is summarized in How can non-aspirin NSAIDs help you? What the research says ›

Improving treatment outcomes: preclinical evidence

Synergistic effects with conventional and complementary therapies

Celecoxib (Celebrex)

• 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.

Indomethacin

• 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.

Noscapine

• 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

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.

Immune function

• 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.

Inflammation

• 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

Cachexia

• 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.