收稿日期: 2024-01-31
网络出版日期: 2024-07-15
基金资助
湖北省自然科学基金项目(2015CFB671)
Research progress of statins in the prevention and treatment of colorectal cancer
Received date: 2024-01-31
Online published: 2024-07-15
汤明欣 , 王晓林 , 李炫飞 . 他汀类药物在结直肠癌防治中的研究进展[J]. 实用医学杂志, 2024 , 40(14) : 2041 -2046 . DOI: 10.3969/j.issn.1006-5725.2024.14.024
Statins, known as hydroxymethylglutaryl coenzyme A reductase (HMG?CoA) inhibitors, are primarily used to lower blood lipids, preventing and treating cardiovascular diseases. Research indicates that statins exhibit multiple effects in the prevention and treatment of colorectal cancer. They function by inhibiting the MVA pathway, suppressing inflammation, enhancing cellular immunity, and influencing the gut microbiota, positively impacting the onset and progression of colorectal cancer. Clinical studies have additionally uncovered that statin drugs can augment the effectiveness of chemotherapy, immunotherapy, and adjuvant therapies, acting as both preventive and adjunctive measures for colorectal cancer. This article critically reviews the research progress on statins in colorectal cancer, aiming to establish a theoretical foundation for exploring innovative treatment options.
Key words: statins; colorectal cancer; prevention and treatment
| 1 | SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin,2021,71(3):209-249. doi:10.3322/caac.21660 |
| 2 | PEPPAS S, PIOVANI D, PEYRIN-BIROULET L, et al. Statins and inflammatory bowel disease: Where do we stand? [J]. Eur J Intern Med,2020,75:10-14. doi:10.1016/j.ejim.2020.02.017 |
| 3 | KATONA B W, WEISS J M. Chemoprevention of Colorectal Cancer [J]. Gastroenterology,2020,158(2):368-388. doi:10.1053/j.gastro.2019.06.047 |
| 4 | DENG C F, ZHU N, ZHAO T J, et al. Involvement of LDL and ox-LDL in Cancer Development and Its Therapeutical Potential [J]. Front Oncol,2022,12:803473. doi:10.3389/fonc.2022.803473 |
| 5 | HAYCOCK P C, BORGES M C, BURROWS K, et al. The association between genetically elevated polyunsaturated fatty acids and risk of cancer [J]. EBioMedicine, 2023, 91: 104510-104510. |
| 6 | BETON-MYSUR K, BRO?EK-P?USKA B. A new modality for cholesterol impact tracking in colon cancer development - Raman imaging, fluorescence and AFM studies combined with chemometric analysis [J]. Anal Methods,2023,15(39):5199-5217. doi:10.1039/d3ay01040f |
| 7 | SHEN C J, CHAN R H, LIN B W, et al. Oleic acid-induced metastasis of KRAS/p53-mutant colorectal cancer relies on concurrent KRAS activation and IL-8 expression bypassing EGFR activation [J]. Theranostics, 2023, 13(13): 4650-4666. doi:10.7150/thno.85855 |
| 8 | JUAREZ D, FRUMAN D A. Targeting the Mevalonate Pathway in Cancer [J]. Trends Cancer, 2021,7(6): 525-540. doi:10.1016/j.trecan.2020.11.008 |
| 9 | FERREIRA A, PEREIRA F, REIS C, et al. Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications [J]. Cells, 2022, 11(14): 2183. doi:10.3390/cells11142183 |
| 10 | GALES L, FORSEA L, MITREA D, et al. Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy [J]. Medicina (Kaunas), 2022, 58(9): 1239. doi:10.3390/medicina58091239 |
| 11 | PAN Q, ZHONG S, WANG H, et al. The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability [J]. Mol Cell, 2021,81(13): 2736-2751.e2738. doi:10.1016/j.molcel.2021.04.009 |
| 12 | XIAO Y, LIU Q, PENG N, et al. Lovastatin Inhibits RhoA to Suppress Canonical Wnt/β-Catenin Signaling and Alternative Wnt-YAP/TAZ Signaling in Colon Cancer [J]. Cell Transplant, 2022, 31: 9636897221075749. doi:10.1177/09636897221075749 |
| 13 | WANG Y N, RUAN D Y, WANG Z X, et al. Targeting the cholesterol-RORα/γ axis inhibits colorectal cancer progression through degrading c-myc [J]. Oncogene,2022,41(49): 5266-5278. doi:10.1038/s41388-022-02515-3 |
| 14 | ZHANG K L, ZHU W W, WANG S H, et al. Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer [J]. Theranostics, 2021,11(13): 6560-6572. doi:10.7150/thno.55609 |
| 15 | ERKINANTTI S, HAUTAKOSKI A, SUND R, et al. The Association of Metformin, Other Antidiabetic Medications and Statins on the Prognosis of Rectal Cancer in Patients with Type 2 Diabetes: A Retrospective Cohort Study [J]. Biomolecules, 2022, 12(9): 1301. doi:10.3390/biom12091301 |
| 16 | SOLIMAN N A, KESHK W A, RIZK F H, et al. The possible ameliorative effect of simvastatin versus sulfasalazine on acetic acid induced ulcerative colitis in adult rats [J]. Chem Biol Interact, 2019, 298: 57-65. doi:10.1016/j.cbi.2018.11.002 |
| 17 | SELVIN T, BERGLUND M, LENHAMMAR L, et al. Phenotypic screening platform identifies statins as enhancers of immune cell-induced cancer cell death [J]. BMC Cancer,2023,23(1): 164. doi:10.1186/s12885-023-10645-4 |
| 18 | HUANG X M, HUANG J J, DU J J, et al. Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin [J]. Acta Pharmacol Sin, 2021, 42(11): 1875-1887. doi:10.1038/s41401-021-00612-9 |
| 19 | CHEN M J, CHENG A C, LEE M F, et al. Simvastatin induces G(1) arrest by up-regulating GSK3β and down-regulating CDK4/cyclin D1 and CDK2/cyclin E1 in human primary colorectal cancer cells [J]. J Cell Physiol, 2018, 233(6): 4618-4625. doi:10.1002/jcp.26156 |
| 20 | BIANCONI V, SAHEBKAR A, ATKIN S L, et al. The regulation and importance of monocyte chemoattractant protein-1 [J]. Curr Opin Hematol, 2018, 25(1): 44-51. doi:10.1097/moh.0000000000000389 |
| 21 | LIU J, HUANG X, LIU H, et al. Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients [J]. J Transl Med, 2021,19(1): 27. doi:10.1186/s12967-020-02638-9 |
| 22 | NAM G H, KWON M, JUNG H, et al. Statin-mediated inhibition of RAS prenylation activates ER stress to enhance the immunogenicity of KRAS mutant cancer [J]. J Immunother Cancer, 2021, 9(7): e002474. doi:10.1136/jitc-2021-002474 |
| 23 | FRAZZI R. BIRC3 and BIRC5: multi-faceted inhibitors in cancer [J]. Cell Biosci, 2021,11(1): 8. doi:10.1186/s13578-020-00521-0 |
| 24 | XIA Y, XIE Y, YU Z, et al. The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery [J]. Cell, 2018, 175(4): 1059-1073.e1021. doi:10.1016/j.cell.2018.08.070 |
| 25 | WHITE M T, SEARS C L. The microbial landscape of colorectal cancer [J]. Nat Rev Microbiol, 2023, 22(4): 240-254. doi:10.1038/s41579-023-00973-4 |
| 26 | HAN J X, TAO Z H, WANG J L, et al. Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer [J]. Nat Microbiol, 2023, 8(5): 919-933. doi:10.1038/s41564-023-01363-5 |
| 27 | CERVANTES-BARRAGAN L, CHAI J N, TIANERO M D, et al. Lactobacillus reuteri induces gut intraepithelial CD4(+)CD8αα(+) T cells [J]. Science, 2017, 357(6353): 806-810. doi:10.1126/science.aah5825 |
| 28 | OKAMOTO K, NOZAWA H, EMOTO S, et al. Does statin suppress oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer?A single-center observational study [J]. Support Care Cancer, 2023, 31(12): 660. doi:10.1007/s00520-023-08134-2 |
| 29 | 黄锐, 刘超, 张艳桥. 辛伐他汀用于结直肠癌治疗的系统综述 [J]. 实用肿瘤学杂志, 2021,35(4): 365-369. doi:10.11904/j.issn.1002-3070.2021.04.013 |
| 30 | XIA J, HE S, DAI Q, et al. Atorvastatin calcium alleviates 5-fluorouracil-induced intestinal damage by inhibiting cellular senescence and significantly enhances its antitumor efficacy [J]. Int Immunopharmacol, 2023, 121: 110465. doi:10.1016/j.intimp.2023.110620 |
| 31 | TSUBAKI M, TAKEDA T, MATSUDA T, et al. Statins enhances antitumor effect of oxaliplatin in KRAS-mutated colorectal cancer cells and inhibits oxaliplatin-induced neuropathy [J]. Cancer Cell Int, 2023, 23(1): 73. doi:10.1186/s12935-023-02884-z |
| 32 | KIM Y, KIM T W, HAN S W, et al. A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients [J]. Cancer Res Treat, 2019, 51(3): 1128-1134. doi:10.4143/crt.2018.379 |
| 33 | YUAN T, WU R, WANG W, et al. Synergistic antitumor activity of regorafenib and rosuvastatin in colorectal cancer [J]. Front Pharmacol, 2023, 14: 1136114. doi:10.3389/fphar.2023.1136114 |
| 34 | NI W, MO H, LIU Y, et al. Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation [J]. Mol Ther, 2021, 29(10): 2995-3010. doi:10.1016/j.ymthe.2021.05.012 |
| 35 | YANG Y, QI J, HU J, et al. Lovastatin/SN38 co-loaded liposomes amplified ICB therapeutic effect via remodeling the immunologically-cold colon tumor and synergized stimulation of cGAS-STING pathway [J]. Cancer Lett, 2024, 588: 216765. doi:10.1016/j.canlet.2024.216765 |
| 36 | BAO H, ZHENG N, LI Z, et al. Synergistic Effect of Tangeretin and Atorvastatin for Colon Cancer Combination Therapy: Targeted Delivery of These Dual Drugs Using RGD Peptide Decorated Nanocarriers [J]. Drug Des Devel Ther, 2020, 14: 3057-3068. doi:10.2147/dddt.s256636 |
| 37 | KARAGKOUNIS G, DEVECCHIO J, FERRANDON S, et al. Simvastatin enhances radiation sensitivity of colorectal cancer cells [J]. Surg Endosc, 2018, 32(3): 1533-1539. doi:10.1007/s00464-017-5841-1 |
| 38 | CAPUTO F, SANTINI C, CASADEI-GARDINI A, et al. Statins increase pathological response in locally advanced rectal cancer treated with chemoradiation: a multicenter experience [J]. Future Oncol, 2022, 18(24): 2651-2659. doi:10.2217/fon-2021-1646 |
| 39 | GASH K J, CHAMBERS A C, COTTON D E, et al. Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy [J]. Br J Cancer, 2017, 117(2): 210-219. doi:10.1038/bjc.2017.175 |
| 40 | FONG W, TO K K W. Drug repurposing to overcome resistance to various therapies for colorectal cancer [J]. Cell Mol Life Sci, 2019, 76(17): 3383-3406. doi:10.1007/s00018-019-03134-0 |
| 41 | OUAHOUD S, JACOBS R J, KODACH L L, et al. Statin use is associated with a reduced incidence of colorectal cancer expressing SMAD4 [J]. Br J Cancer, 2022, 126(2): 297-301. doi:10.1038/s41416-021-01604-6 |
| 42 | MARRONE M T, MONDUL A M, PRIZMENT A E, et al. Lipid-Lowering Drug Use and Cancer Incidence and Mortality in the ARIC Study [J]. JNCI Cancer Spectr, 2021, 5(5): pkab080. doi:10.1093/jncics/pkab080 |
| 43 | RODRíGUEZ-MIGUEL A, FERNáNDEZ-ANTóN E, BARRE-IRA-HERNáNDEZ D, et al. Statins and Colorectal Cancer Risk: A Population-Based Case-Control Study and Synthesis of the Epidemiological Evidence [J]. J Clin Med, 2022, 11(6): 1528. doi:10.3390/jcm11061528 |
| 44 | SUN J, HALFVARSON J, BERGMAN D, et al. Statin use and risk of colorectal cancer in patients with inflammatory bowel disease [J]. EClinicalMedicine, 2023, 63: 102182. doi:10.1016/j.eclinm.2023.102182 |
| 45 | LI Y, HE X, DING Y, et al. Statin uses and mortality in colorectal cancer patients: An updated systematic review and meta-analysis [J]. Cancer Med, 2019, 8(6): 3305-3313. doi:10.1002/cam4.2151 |
| 46 | POURLOTFI A, BASS G A, HULME R AHL, et al. Statin Use and Long-Term Mortality after Rectal Cancer Surgery [J]. Cancers (Basel), 2021, 13(17): 4288. doi:10.3390/cancers13174288 |
| 47 | POURLOTFI A, HULME R AHL, FORSSTEN M P, et al. Statin therapy and its association with long-term survival after colon cancer surgery [J]. Surgery, 2022, 171(4): 890-896. doi:10.1016/j.surg.2021.08.002 |
| 48 | ARAI J, SUZUKI N, NIIKURA R, et al. Chemoprevention for Colorectal Cancers: Are Chemopreventive Effects Different Between Left and Right Sided Colorectal Cancers? [J]. Dig Dis Sci, 2022, 67(11): 5227-5238. doi:10.1007/s10620-022-07431-w |
| 49 | ZHANG Y, WU K, CHAN A T, et al. Long-Term Statin Use, Total Cholesterol Level, and Risk of Colorectal Cancer: A Prospective Cohort Study [J]. Am J Gastroenterol, 2022, 117(1): 158-166. doi:10.14309/ajg.0000000000001543 |
| 50 | JEONG G H, LEE K H, KIM J Y, et al. Statin and Cancer Mortality and Survival: An Umbrella Systematic Review and Meta-Analysis [J]. J Clin Med, 2020, 9(2): 326. doi:10.3390/jcm9020326 |
| 51 | MIN Y, WEI X, LIU Z, et al. Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study [J]. Front Pharmacol, 2023, 14: 1109580. doi:10.3389/fphar.2023.1109580 |
/
| 〈 |
|
〉 |