The Inhibitory Effects of Propofol on Colorectal Cancer Progression through the NF-κB/HIF-1α Signaling Pathway


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Background and Objective:Colorectal cancer (CRC) is a neoplastic disease that gradually develops due to genetic variations and epigenetic changes. Surgical excision is the first-line treatment for CRC. Accumulating evidence has shown that total intravenous anesthesia has beneficial effects for CRC patients as it decreases the probability of tumor recurrence and metastasis. Propofol is one of the most frequently used intravenous anesthetics in clinical practice. However, it remains unknown whether it can reduce recurrence and metastasis after surgery in cancer patients.

Methods:CRC cell lines (HCT116 and SW480) were cultured in vitro, and different concentrations of propofol were added to the cell culture medium. The proliferation effect of propofol on CRC cell lines was evaluated by CCK-8 assay. The effect of propofol on the migration and invasion of CRC cells was evaluated by scratch healing and Transwell experiments. The inhibitory effects of propofol on NF-κB and HIF-1α expressions in CRC cell lines were determined by Western blotting and immunofluorescence assays to further clarify the regulatory effects of propofol on NF-κB and HIF-1α.

Results:Compared to the control, propofol significantly inhibited the proliferation, migration, and invasion abilities of CRC cells (HCT116 and SW480) (p < 0.0001). The expression levels of NF-κB and HIF-1α gradually decreased with increasing propofol concentration in both cell lines. After activation and inhibition of NF-κB, the expression of HIF-1α changed. Further studies showed that propofol inhibited LPS-activated NF-κB-induced expression of HIF-1α, similar to the NF-κB inhibitor Bay17083 (p < 0.0001).

Conclusion:In vitro, propofol inhibited the proliferation, migration, and invasion of CRC cells (HCT116 and SW480) in a dose-dependent manner, possibly by participating in the regulation of the NF-κB/HIF-1α signaling pathway.

Sobre autores

Liuxu Yao

Department of Anesthesiology, Affiliated People's Hospital, Hangzhou Medical College

Email: info@benthamscience.net

Wen Zhai

Department of Anesthesiology, Affiliated People's Hospital, Hangzhou Medical College

Email: info@benthamscience.net

Zongming Jiang

Department of Anesthesiology, Shaoxing People’s Hospital

Email: info@benthamscience.net

Rui He

Department of Anesthesiology, Shaoxing People’s Hospital

Email: info@benthamscience.net

Weiying Xie

Department of Anesthesiology, Affiliated People's Hospital, Hangzhou Medical College

Email: info@benthamscience.net

Yuhong Li

Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren College

Autor responsável pela correspondência
Email: info@benthamscience.net

Yiyang Hu

Department of Anesthesiology, Affiliated People's Hospital, Hangzhou Medical College

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249. doi: 10.3322/caac.21660 PMID: 33538338
  2. Zygulska, A.L.; Pierzchalski, P. Novel diagnostic biomarkers in colorectal cancer. Int. J. Mol. Sci., 2022, 23(2), 852. doi: 10.3390/ijms23020852 PMID: 35055034
  3. Shin, A.E.; Giancotti, F.G.; Rustgi, A.K. Metastatic colorectal cancer: Mechanisms and emerging therapeutics. Trends Pharmacol. Sci., 2023, 44(4), 222-236. doi: 10.1016/j.tips.2023.01.003 PMID: 36828759
  4. Galema, H.A.; Meijer, R.P.J.; Lauwerends, L.J.; Verhoef, C.; Burggraaf, J.; Vahrmeijer, A.L.; Hutteman, M.; Keereweer, S.; Hilling, D.E. Fluorescence-guided surgery in colorectal cancer; A review on clinical results and future perspectives. Eur. J. Surg. Oncol., 2022, 48(4), 810-821. doi: 10.1016/j.ejso.2021.10.005 PMID: 34657780
  5. Leowattana, W.; Leowattana, P.; Leowattana, T. Systemic treatment for metastatic colorectal cancer. World J. Gastroenterol., 2023, 29(10), 1569-1588. doi: 10.3748/wjg.v29.i10.1569 PMID: 36970592
  6. Faroni, E.; Sabattini, S.; Lenzi, J.; Guerra, D.; Comazzi, S.; Aresu, L.; Mazzanti, A.; Zanardi, S.; Cola, V.; Lotito, E.; Marconato, L. Sleeping beauty: Anesthesia may promote relapse in dogs with diffuse large B-Cell lymphoma in complete remission after Chemo-Immunotherapy. Front. Vet. Sci., 2021, 8, 760603. doi: 10.3389/fvets.2021.760603 PMID: 34881319
  7. Cascella, M.; Cuomo, A.; Bifulco, F.; Perri, F.; Carbone, F.; Aprea, M.; Forte, C.A.; Fiore, M. Could the perioperative use of opioids influence cancer outcomes after surgery? A scoping review protocol. BMJ Open, 2022, 12(3), e054520. doi: 10.1136/bmjopen-2021-054520 PMID: 35292495
  8. Perry, N.J.S.; Buggy, D.; Ma, D. Can anesthesia influence cancer outcomes after surgery? JAMA Surg., 2019, 154(4), 279-280. doi: 10.1001/jamasurg.2018.4619 PMID: 30649136
  9. Walsh, C.T. Propofol: Milk of amnesia. Cell, 2018, 175(1), 10-13. doi: 10.1016/j.cell.2018.08.031 PMID: 30217361
  10. Xu, Y.; Pan, S.; Jiang, W.; Xue, F.; Zhu, X. Effects of propofol on the development of cancer in humans. Cell Prolif., 2020, 53(8), e12867. doi: 10.1111/cpr.12867 PMID: 32596964
  11. Ramirez, M.F.; Gan, T.J. Total intravenous anesthesia versus inhalation anesthesia: How do outcomes compare? Curr. Opin. Anaesthesiol., 2023, 36(4), 399-406. doi: 10.1097/ACO.0000000000001274 PMID: 37338939
  12. Chang, C.Y.; Wu, M.Y.; Chien, Y.J.; Su, I.M.; Wang, S.C.; Kao, M.C. Anesthesia and long-term oncological outcomes: A systematic review and meta-analysis. Anesth. Analg., 2021, 132(3), 623-634. doi: 10.1213/ANE.0000000000005237 PMID: 33105278
  13. Fang, P.; Zhou, J.; Xia, Z.; Lu, Y.; Liu, X. Effects of propofol versus sevoflurane on postoperative breast cancer prognosis: A narrative review. Front. Oncol., 2022, 11, 793093. doi: 10.3389/fonc.2021.793093 PMID: 35127500
  14. Zhao, R.; Xu, X.; Sun, L.; Zhang, G. Long-term effect of anesthesia choice on patients with hepatocellular carcinoma undergoing open liver resection. Front. Oncol., 2023, 12, 960299. doi: 10.3389/fonc.2022.960299 PMID: 36713494
  15. Lu, X.; Yu, Y.; Wang, Y.; Lyu, Y. Effect of propofol or etomidate as general anaesthesia induction on gastric cancer: A retrospective cohort study with 10 years’ follow-up. Cancer Manag. Res., 2022, 14, 2399-2407. doi: 10.2147/CMAR.S361052 PMID: 35967754
  16. Zhou, X.; Shao, Y.; Li, S.; Zhang, S.; Ding, C.; Zhuang, L.; Sun, J. An intravenous anesthetic drug-propofol, influences the biological characteristics of malignant tumors and reshapes the tumor microenvironment: A narrative literature review. Front. Pharmacol., 2022, 13, 1057571. doi: 10.3389/fphar.2022.1057571 PMID: 36506511
  17. Wang, R.; Li, S.; Hou, Q.; Zhang, B.; Chu, H.; Hou, Y.; Ni, C.; Sun, L.; Ran, Y.; Zheng, H. Propofol inhibits colon cancer cell stemness and epithelial-mesenchymal transition by regulating SIRT1, Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Discover Oncology, 2023, 14(1), 137. doi: 10.1007/s12672-023-00734-y PMID: 37490168
  18. Capece, D.; Verzella, D.; Flati, I.; Arboretto, P.; Cornice, J.; Franzoso, G. NF-κB: Blending metabolism, immunity, and inflammation. Trends Immunol., 2022, 43(9), 757-775. doi: 10.1016/j.it.2022.07.004 PMID: 35965153
  19. O’Donnell, A.; Pepper, C.; Mitchell, S.; Pepper, A. NF-kB and the CLL microenvironment. Front. Oncol., 2023, 13, 1169397. doi: 10.3389/fonc.2023.1169397 PMID: 37064123
  20. Kaltschmidt, B.; Witte, K.E.; Greiner, J.F.W.; Weissinger, F.; Kaltschmidt, C. Targeting NF-κB signaling in cancer stem cells: A narrative review. Biomedicines, 2022, 10(2), 261. doi: 10.3390/biomedicines10020261 PMID: 35203471
  21. Rong, D.; Sun, G.; Zheng, Z.; Liu, L.; Chen, X.; Wu, F.; Gu, Y.; Dai, Y.; Zhong, W.; Hao, X.; Zhang, C.; Pan, X.; Tang, J.; Tang, W.; Wang, X. MGP promotes CD8 + T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer. Int. J. Biol. Sci., 2022, 18(6), 2345-2361. doi: 10.7150/ijbs.70137 PMID: 35414780
  22. Wang, Z.; Sun, X.; Feng, Y.; Wang, Y.; Zhang, L.; Wang, Y.; Fang, Z.; Azami, N.L.B.; Sun, M.; Li, Q. Dihydromyricetin reverses MRP2-induced multidrug resistance by preventing NF-κB-Nrf2 signaling in colorectal cancer cell. Phytomedicine, 2021, 82, 153414. doi: 10.1016/j.phymed.2020.153414 PMID: 33461143
  23. Xin, Y.; Zhao, L.; Peng, R. HIF-1 signaling: An emerging mechanism for mitochondrial dynamics. J. Physiol. Biochem., 2023, 79(3), 489-500. doi: 10.1007/s13105-023-00966-0 PMID: 37178248
  24. Vatte, S.; Ugale, R. HIF-1, an important regulator in potential new therapeutic approaches to ischemic stroke. Neurochem. Int., 2023, 170, 105605. doi: 10.1016/j.neuint.2023.105605 PMID: 37657765
  25. Negri, A.L. Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification. Clin. Kidney J., 2023, 16(2), 205-209. doi: 10.1093/ckj/sfac224 PMID: 36755843
  26. Sharma, D.; Khan, H.; Kumar, A.; Grewal, A.K.; Dua, K.; Singh, T.G. Pharmacological modulation of HIF-1 in the treatment of neuropsychiatric disorders. J. Neural Transm. , 2023, 130(12), 1523-1535. doi: 10.1007/s00702-023-02698-3 PMID: 37740098
  27. Korbecki, J.; Simińska, D.; Dobrowolska, G.M.; Listos, J.; Gutowska, I.; Chlubek, D.; Bosiacka, B.I. Chronic and cycling hypoxia: Drivers of cancer chronic inflammation through HIF-1 and NF-κB activation: A review of the molecular mechanisms. Int. J. Mol. Sci., 2021, 22(19), 10701. doi: 10.3390/ijms221910701 PMID: 34639040
  28. Gupta, S.; May, F.P.; Kupfer, S.S.; Murphy, C.C. Birth Cohort Colorectal Cancer (CRC): Implications for research and practice. Clin. Gastroenterol. Hepatol., 2024, 22(3), 455-469.e7. doi: 10.1016/j.cgh.2023.11.040 PMID: 38081492
  29. Kasprzak, A. Prognostic biomarkers of cell proliferation in colorectal cancer (CRC): From immunohistochemistry to molecular biology techniques. Cancers , 2023, 15(18), 4570. doi: 10.3390/cancers15184570 PMID: 37760539
  30. Yan, R.; Song, T.; Wang, W.; Tian, J.; Ma, X. Immunomodulatory roles of propofol and sevoflurane in murine models of breast cancer. Immunopharmacol. Immunotoxicol., 2023, 45(2), 153-159. doi: 10.1080/08923973.2022.2122501 PMID: 36073191
  31. Wang, J.; Cheng, C.; Lu, Y.; Ding, X.; Zhu, M.; Miao, C.; Chen, J. Novel findings of anti-cancer property of propofol. Anticancer. Agents Med. Chem., 2018, 18(2), 156-165. doi: 10.2174/1871520617666170912120327 PMID: 28901262
  32. Zhan, K.; Song, X.; Zhang, Q.; Yang, J.; Lu, S. Propofol-induced miR-493-3p inhibits growth and invasion of gastric cancer through suppression of DKK1-mediated Wnt/β-Catenin signaling activation. Dis. Markers, 2023, 2023, 1-8. doi: 10.1155/2023/7698706 PMID: 36762306
  33. Wu, J.; Zhou, F.; Lai, S.; Wang, W.; Wu, T.; Liu, Y.; Yang, L. Propofol inhibits biological function of hepatocellular carcinoma cells through LINC00475-mediated sonic hedgehog pathway. Pharmacology, 2023, 108(2), 127-137. doi: 10.1159/000527200 PMID: 36516819
  34. Gao, Y.; Zhou, Y.; Wang, C.; Sample, K.; Yu, X.; Ben-David, Y. Propofol mediates pancreatic cancer cell activity through the repression of ADAM8 via SP1. Oncol. Rep., 2021, 46(6), 249. doi: 10.3892/or.2021.8200 PMID: 34617574
  35. Zhou, R.; Konishi, Y.; Zhang, A.; Nishiwaki, K. Propofol elicits apoptosis and attenuates cell growth in esophageal cancer cell lines. Nagoya J. Med. Sci., 2023, 85(3), 579-591. doi: 10.18999/nagjms.85.3.579 PMID: 37829490
  36. Wang, Y.; Xu, B.; Zhou, J.; Wu, X. Propofol activates AMPK to inhibit the growth of HepG2 cells in vitro and hepatocarcinogenesis in xenograft mouse tumor models by inducing autophagy. J. Gastrointest. Oncol., 2020, 11(6), 1322-1332. doi: 10.21037/jgo-20-472 PMID: 33457004
  37. Xu, W.; He, Y.; Wang, Y.; Li, X.; Young, J.; Ioannidis, J.P.A.; Dunlop, M.G.; Theodoratou, E. Risk factors and risk prediction models for colorectal cancer metastasis and recurrence: An umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med., 2020, 18(1), 172. doi: 10.1186/s12916-020-01618-6 PMID: 32586325
  38. Zhang, X.; He, C.; Xiang, G. Engineering nanomedicines to inhibit hypoxia-inducible Factor-1 for cancer therapy. Cancer Lett., 2022, 530, 110-127. doi: 10.1016/j.canlet.2022.01.012 PMID: 35041892
  39. Li, Z.; Wei, R.; Yao, S.; Meng, F.; Kong, L. HIF-1A as a prognostic biomarker related to invasion, migration and immunosuppression of cervical cancer. Heliyon, 2024, 10(2), e24664. doi: 10.1016/j.heliyon.2024.e24664 PMID: 38298716
  40. Xu, Y.; Kuai, R.; Chu, Y.M.; Zhou, L.; Zhang, H.Q.; Li, J. Hypoxia facilitates the proliferation of colorectal cancer cells by inducing cancer-associated fibroblast-derived IL6. Neoplasma, 2021, 68(5), 1015-1022. doi: 10.4149/neo_2021_210308N296 PMID: 34374296
  41. Bian, Y.; Yin, G.; Wang, G.; Liu, T.; Liang, L.; Yang, X. Degradation of HIF-1α induced by curcumol blocks glutaminolysis and inhibits epithelial-mesenchymal transition and invasion in colorectal cancer cells. Cell Biol. Toxicol., 2023, 39(5), 1957-1978. doi: 10.1007/s10565-021-09681-2 PMID: 35083610
  42. Zhang, Y.; Chai, N.; Wei, Z.; Li, Z.; Zhang, L.; Zhang, M.; Ren, J.; Xu, R.; Pang, X.; Zhang, B.; Tang, Q.; Sui, H. YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro. Phytomedicine, 2022, 98, 153917. doi: 10.1016/j.phymed.2021.153917 PMID: 35093671
  43. Aqdas, M.; Sung, M.H. NF-κB dynamics in the language of immune cells. Trends Immunol., 2023, 44(1), 32-43. doi: 10.1016/j.it.2022.11.005 PMID: 36473794
  44. Kordahi, M.C.; Stanaway, I.B.; Avril, M.; Chac, D.; Blanc, M.P.; Ross, B.; Diener, C.; Jain, S.; McCleary, P.; Parker, A.; Friedman, V.; Huang, J.; Burke, W.; Gibbons, S.M.; Willis, A.D.; Darveau, R.P.; Grady, W.M.; Ko, C.W.; DePaolo, R.W. Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer. Cell Host Microbe, 2021, 29(10), 1589-1598.e6. doi: 10.1016/j.chom.2021.08.013 PMID: 34536346
  45. Deka, K.; Li, Y. Transcriptional regulation during aberrant activation of NF-κB signalling in cancer. Cells, 2023, 12(5), 788. doi: 10.3390/cells12050788 PMID: 36899924
  46. Rastogi, S.; Aldosary, S.; Saeedan, A.S.; Ansari, M.N.; Singh, M.; Kaithwas, G. NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment. Front. Pharmacol., 2023, 14, 1108915. doi: 10.3389/fphar.2023.1108915 PMID: 36891273
  47. Li, Z.L.; Ji, J.L.; Wen, Y.; Cao, J.Y.; Kharbuja, N.; Ni, W.J.; Yin, D.; Feng, S.T.; Liu, H.; Lv, L.L.; Liu, B.C.; Wang, B. HIF-1α is transcriptionally regulated by NF-κB in acute kidney injury. Am. J. Physiol. Renal Physiol., 2021, 321(2), F225-F235. doi: 10.1152/ajprenal.00119.2021 PMID: 34229478
  48. Liu, X.; Gao, Z.; Wang, X.; Shen, Y. Parthenolide targets NF-κB (P50) to inhibit HIF-1α-mediated metabolic reprogramming of HCC. Aging , 2022, 14(20), 8346-8356. doi: 10.18632/aging.204339 PMID: 36260873
  49. Huang, X.; Teng, Y.; Yang, H.; Ma, J. Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-κB signal. Braz. J. Med. Biol. Res., 2016, 49(12), e5717. doi: 10.1590/1414-431x20165717 PMID: 27982283
  50. Ling, Q.; Wu, S.; Liao, X.; Liu, C.; Chen, Y. Anesthetic propofol enhances cisplatin-sensitivity of non-small cell lung cancer cells through N6-methyladenosine-dependently regulating the miR-486-5p/RAP1-NF-κB axis. BMC Cancer, 2022, 22(1), 765. doi: 10.1186/s12885-022-09848-y PMID: 35836137
  51. Reiner, G.N.; Perillo, M.A.; García, D.A. Effects of propofol and other GABAergic phenols on membrane molecular organization. Colloids Surf. B Biointerfaces, 2013, 101, 61-67. doi: 10.1016/j.colsurfb.2012.06.004 PMID: 22796773
  52. Irifune, M.; Takarada, T.; Shimizu, Y.; Endo, C.; Katayama, S.; Dohi, T.; Kawahara, M. Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric acid-A and excitatory amino acid receptors. Anesth. Analg., 2003, 97(2), 424-429. doi: 10.1213/01.ANE.0000059742.62646.40 PMID: 12873929
  53. Ribeiro, M.P.C.; Custódio, J.B.A.; Santos, A.E. Ionotropic glutamate receptor antagonists and cancer therapy: Time to think out of the box? Cancer Chemother. Pharmacol., 2017, 79(2), 219-225. doi: 10.1007/s00280-016-3129-0 PMID: 27586965
  54. Zhang, D.; Li, X.; Yao, Z.; Wei, C.; Ning, N.; Li, J. GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation. Cancer Lett., 2014, 348(1-2), 100-108. doi: 10.1016/j.canlet.2014.03.006 PMID: 24657659
  55. Zhang, Q.; Wang, L.; Chen, B.; Zhuo, Q.; Bao, C.; Lin, L. Propofol inhibits NF-κB activation to ameliorate airway inflammation in ovalbumin (OVA)-induced allergic asthma mice. Int. Immunopharmacol., 2017, 51, 158-164. doi: 10.1016/j.intimp.2017.08.015 PMID: 28843179
  56. Yang, N.; Liang, Y.; Yang, P.; Ji, F. Propofol suppresses LPS-induced nuclear accumulation of HIF-1α and tumor aggressiveness in non-small cell lung cancer. Oncol. Rep., 2017, 37(5), 2611-2619. doi: 10.3892/or.2017.5514 PMID: 28426124

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