The effects of curcumin on the biological behavior of colorectal cancer cells through the JAK/STAT3 and RAS/MAPK/NF-κB pathways.
Los efectos de la curcumina en el comportamiento biológico de las células del cáncer colorrectal mediante las vías JAK/STAT3 y RAS/MAPK/NF-KB.
Abstract
The purpose of this work was to investigate the effects of curcumin on the biological behavior of colorectal cancer cells through the JAK/STAT3 and RAS/MAPK/NF-κB pathways. Human colorectal cancer HCT116 cells were cultured and divided into a control group and low, medium and high-dose curcumin groups (n =5). HCT116 colorectal cancer cells became long-growing cells after incubation and culture at 37°C. The control group was treated with 15μL phosphate-buffered saline, and the low-dose, medium-dose and high-dose curcumin groups were treated with 20, 40 and 80μmol/L curcumin, respectively. All groups were treated with relevant drug intervention, digested and centrifuged for 48h, washed twice with a PBS solution, centrifuged at 1000 rpm for 3 min, and the cells precipitated. The proliferation, apoptosis and growth cycle of cells in each group were observed, and the expressions of the JAK/STAT3 and RAS/MAPK/NF-κB pathways and related proteins in each group were studied. Compared with the curcumin low-dose and medium-dose groups, the proliferation ability of the curcumin high-dose group was significantly decreased (P<0.05). When the low-dose and medium-dose curcumin groups were compared with the high-dose curcumin group, the apoptosis ability was significantly increased (P<0.05). When the low-dose and medium-dose curcumin groups were compared, the growth ratio of the G0/G1 phase in the high-dose curcumin group was significantly increased, and the percentage of the S phase was significantly decreased (P<0.05). Compared with the curcumin low-dose and medium-dose groups, the expression of JAK-STAT3 and RAS/MAPK/NF-κB pathway in the curcumin high-dose group was significantly decreased (P<0.05). The protein expressions of STAT3, RAS, P-P38 and P65 in the curcumin high-dose group were significantly lower than those in the curcumin low-dose and medium-dose groups (P<0.05). Curcumin can inhibit the expression of JAK/STAT3 and RAS/MAPK/NF-κB pathways, block the growth cycle, and inhibit the proliferation and induce apoptosis of colorectal cancer cells, providing a new idea for the clinical treatment of colorectal cancer.
Downloads
References
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66(4):683-691.
Zhang Y, Hou Y, Zhang D. Effects of TYMP gene polymorphism on adjuvant chemotherapy after R0 resection in patients with colorectal cancer. Cancer Res 2018; 45(7): 5.
Chiu HC, Lin YC, Hsieh HM, Chen HP, Wang HL, Wang JY. The impact of complications on prolonged length of hospital stay after resection in colorectal cancer: A retrospective study of Taiwanese patients. J Int Med Res 2017; 45(2): 691-705.
Li XJ. Basic and clinical research and problems of curcumin in tumor therapy. Chinese J Pharmacol Toxicol 2019; 33(9): 2.
Zhang L, Pan H, Wang Y, Guo T, Liu L. Genome profiling revealed the activation of IL2RG/JAK3/STAT5 in peripheral T‑cell lymphoma expressing the ITK‑SYK fusion gene. Int J Oncol 2019; 55(5): 1077-1089.
Lu J, Fu X, Zhang JH, Chen H,Gao J, Fan J, Zhang Y. Changes of tumor necrosis factor -α/P38 mitogen-activated protein kinase/serum nuclear factor -κB/ retinol binding protein signaling pathway in ApoE gene knockout mice. Anhui Med Pharm J 2018; 22(7): 5. Barkovits K, Pfeiffer K, Eggers B, Marcus
K. Protein Quantification Using the “Rapid Western Blot” Approach. InQuantitative Methods in Proteomics 2021 (pp. 29-39). Humana, New York, NY.
Majtnerová P, Roušar T. An overview of apoptosis assays detecting DNA fragmentation. Molecular biology reports 2018 Oct;45(5):1469-1478.
National Clinical Research Center for Digestive Diseases (Shanghai), National Alliance of Centers for Prevention and Treatment of Early Gastrointestinal Cancer, Chinese Society of Digestive Endoscopy, Health Management Branch of Chinese Medical Association. A review of early colorectal cancer screening in China. National Med J China 2019; 99(38): 2961-2970. DOI: 10.3760/cma.j.is sn.0376-2491.2019.38.001.
Zhang H, You J, Liu W, Chen D, Zhang S, Wang X. The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis. Medicine (Baltimore) 2021; 100(30). :e26714.
Li N, Wang XT, Jiang SH, Zhang SN, Wang D. Preparation and antitumor activity evaluation of curcumin precursor. China Coal Ind Med J 2017; 20(7): 3. DOI: 10.13422/j.cnki.syfjx.20181891.
Sun W. The effect of curcumin on the biological behavior of human thyroid cancer b- CPAP cells. Mod Oncol 2019; 27(2): 5.
Guo Y, Hua C, Yu X, Pei X, Li Y. Effects of curcumin on tPC-1 proliferation, apoptosis, migration and invasion of thyroid cancer cells by regulating Mir-152. J Guangxi Med Univ 2021; 38(7): 7.
Wu CS, Wu SY, Chen HC, Chu CA, Tang HH, Liu H SH, Hong Y, Huang CY, Huang GC, Su CL. Curcumin functions as a MEK inhibitor to induce a synthetic lethal effect on KRAS mutant colorectal cancer cells receiving targeted drug regorafenib. J Nutr Biochem 2019; 74: 108227.
Yang L, Hong L. Integrin β 1-fak-RAS-MAPK signal transduction pathway and its relationship with tumor. China Med Rev 2019; 16(30): 4.
Wu Z, Liu H, Sun W, Du Y, He W, Guo Sh, Chen L, Zhao Zh, Wang P, Liang H, Deng J. RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells. Cell Death Dis 2020; 11(10): 1-11.
Liu LP, Hao JY, Pan H, Wang C, Yue P. Mutation of RAS gene in thyroid follicular differentiated tumor and its significance. Chinese J Pathol 2020; 49(3): 6.
Yu Peng, Yan S. Effects of simulated hypoxic microenvironment on invasion, migration and Ras/MAPK/NF-κB pathway of human gastric cancer cells. China Clin Res 2019; 32(7): 5.
