MG132-mediated Suppression of the Ubiquitin-proteasome Pathway Enhances the Sensitivity of Endometrial Cancer Cells to Cisplatin


Цитировать

Полный текст

Аннотация

Result:MG132 exposure significantly reduced cell viability in a dose-dependent manner. It augmented cisplatin- induced proliferation inhibition and enhanced apoptosis, correlating with caspase-3 activation and ROS upregulation. Molecular analysis revealed a profound inhibition of the ubiquitin-proteasome system. MG132 also significantly increased the expression of cisplatin-induced pro-inflammatory cytokines, suggesting a transition from chronic to acute inflammation.

Background:Tumor cell resistance to cisplatin is a common challenge in endometrial cancer chemotherapy, stemming from various mechanisms. Targeted therapies using proteasome inhibitors, such as MG132, have been investigated to enhance cisplatin sensitivity, potentially offering a novel treatment approach.

Objective:The aim of this study was to investigate the effects of MG132 on cisplatin sensitivity in the human endometrial cancer (EC) cell line RL95-2, focusing on cell proliferation, apoptosis, and cell signaling.

Methods:Human endometrial cancer RL95-2 cells were exposed to MG132, and cell viability was assessed in a dose-dependent manner. The study evaluated the effect of MG132 on cisplatin-induced proliferation inhibition and apoptosis, correlating with caspase-3 activation and reactive oxygen species (ROS) upregulation. Additionally, we examined the inhibition of the ubiquitin-proteasome system and the expression of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and IL-13 during MG132 and cisplatin co-administration.

Results:Human endometrial cancer RL95-2 cells were exposed to MG132, and cell viability was assessed in a dose-dependent manner. The study evaluated the effect of MG132 on cisplatin-induced proliferation inhibition and apoptosis, correlating with caspase-3 activation and reactive oxygen species (ROS) upregulation. Additionally, we examined the inhibition of the ubiquitin-proteasome system and the expression of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and IL-13 during MG132 and cisplatin co-administration.

Conclusion:MG132 enhances the therapeutic efficacy of cisplatin in human EC cells by suppressing the ubiquitin- proteasome pathway, reducing cell viability, enhancing apoptosis, and shifting the inflammatory response. These findings highlighted the potential of MG132 as an adjuvant in endometrial cancer chemotherapy. Further research is needed to explore detailed mechanisms and clinical applications of this combination therapy.

Об авторах

Zhanhu Zhang

Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Health Care Hospital of Nantong University

Email: info@benthamscience.net

Yiqian Ding

Department of Gynaecology, Affiliated Maternity and Child Health Care Hospital of Nantong University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Xie, W.; Liu, N.; Wang, X.; Wei, L.; Xie, W.; Sheng, X. Wilms’ tumor 1-associated protein contributes to chemo-resistance to cisplatin through the Wnt/β-catenin pathway in endometrial cancer. Front. Oncol., 2021, 11, 598344. doi: 10.3389/fonc.2021.598344 PMID: 33680959
  2. Qiang, W.; Sui, F.; Ma, J.; Li, X.; Ren, X.; Shao, Y.; Liu, J.; Guan, H.; Shi, B.; Hou, P. Proteasome inhibitor MG132 induces thyroid cancer cell apoptosis by modulating the activity of transcription factor FOXO3a. Endocrine, 2017, 56(1), 98-108. doi: 10.1007/s12020-017-1256-y PMID: 28220348
  3. Lee, H.K.; Park, S.H.; Nam, M.J. Proteasome inhibitor MG132 induces apoptosis in human osteosarcoma U2OS cells. Hum. Exp. Toxicol., 2021, 40(11), 1985-1997. doi: 10.1177/09603271211017972 PMID: 34002651
  4. Zheng, Z.; Wang, X.; Chen, D. Proteasome inhibitor MG132 enhances the sensitivity of human OSCC cells to cisplatin via a ROS/DNA damage/p53 axis. Exp. Ther. Med., 2023, 25(5), 224. doi: 10.3892/etm.2023.11924 PMID: 37123203
  5. Sun, F.; Zhang, Y.; Xu, L.; Li, S.; Chen, X.; Zhang, L.; Wu, Y.; Li, J. Proteasome inhibitor MG132 enhances cisplatin-induced apoptosis in osteosarcoma cells and inhibits tumor growth. Oncol. Res., 2018, 26(4), 655-664. doi: 10.3727/096504017X15119525209765 PMID: 29191257
  6. Park, J.; Cho, J.; Song, E.J. Ubiquitin–proteasome system (UPS) as a target for anticancer treatment. Arch. Pharm. Res., 2020, 43(11), 1144-1161. doi: 10.1007/s12272-020-01281-8 PMID: 33165832
  7. Sahasrabuddhe, A.A.; Elenitoba-Johnson, K.S.J. Role of the ubiquitin proteasome system in hematologic malignancies. Immunol. Rev., 2015, 263(1), 224-239. doi: 10.1111/imr.12236 PMID: 25510280
  8. Li, Y.; Li, S.; Wu, H. Ubiquitination-proteasome system (UPS) and autophagy two main protein degradation machineries in response to cell stress. Cells, 2022, 11(5), 851. doi: 10.3390/cells11050851 PMID: 35269473
  9. Wu, H.Q.; Baker, D.; Ovaa, H. Small molecules that target the ubiquitin system. Biochem. Soc. Trans., 2020, 48(2), 479-497. doi: 10.1042/BST20190535 PMID: 32196552
  10. Sharma, A.; Khan, H.; Singh, T.; Grewal, A.; Najda, A.; Kawecka-Radomska, M.; Kamel, M.; Altyar, A.; Abdel-Daim, M. Pharmacological modulation of ubiquitin-proteasome pathways in oncogenic signaling. Int. J. Mol. Sci., 2021, 22(21), 11971. doi: 10.3390/ijms222111971 PMID: 34769401
  11. Morgan, J.J.; Crawford, L.J. The ubiquitin proteasome system in genome stability and cancer. Cancers (Basel), 2021, 13(9), 2235. doi: 10.3390/cancers13092235 PMID: 34066546
  12. Bu, Z.; Yang, J.; Zhang, Y.; Luo, T.; Fang, C.; Liang, X.; Peng, Q.; Wang, D.; Lin, N.; Zhang, K.; Tang, W. Sequential ubiquitination and phosphorylation epigenetics reshaping by MG132‐loaded Fe‐MOF disarms treatment resistance to repulse metastatic colorectal cancer. Adv. Sci. (Weinh.), 2023, 10(23), 2301638. doi: 10.1002/advs.202301638 PMID: 37303273
  13. Behl, T.; Chadha, S.; Sachdeva, M.; Kumar, A.; Hafeez, A.; Mehta, V.; Bungau, S. Ubiquitination in rheumatoid arthritis. Life Sci., 2020, 261, 118459. doi: 10.1016/j.lfs.2020.118459 PMID: 32961230
  14. Liu, F.; Gao, X.; Yu, H.; Yuan, D.; Zhang, J.; He, Y.; Yue, L. Effects of expression of exogenous cyclin G1 on proliferation of human endometrial carcinoma cells. Chin. J. Physiol., 2013, 56(2), 83-89. doi: 10.4077/CJP.2013.BAA079 PMID: 23589924
  15. Papa, L.; Gomes, E.; Rockwell, P. Reactive oxygen species induced by proteasome inhibition in neuronal cells mediate mitochondrial dysfunction and a caspase-independent cell death. Apoptosis, 2007, 12(8), 1389-1405. doi: 10.1007/s10495-007-0069-5 PMID: 17415663
  16. Llobet, D.; Eritja, N.; Encinas, M.; Sorolla, A.; Yeramian, A.; Schoenenberger, J.A.; Llombart-Cussac, A.; Marti, R.M.; Matias-Guiu, X.; Dolcet, X. Antioxidants block proteasome inhibitor function in endometrial carcinoma cells. Anticancer Drugs, 2008, 19(2), 115-124. doi: 10.1097/CAD.0b013e3282f24031 PMID: 18176107
  17. Ma, J.; Yu, L.; Tian, J.; Mu, Y.; Lv, Z.; Zou, J.; Li, J.; Wang, H.; Xu, W. MG132 reverse the malignant characteristics of hypopharyngeal cancer. Mol. Med. Rep., 2014, 9(6), 2587-2591. doi: 10.3892/mmr.2014.2103 PMID: 24691740
  18. Han, Y.H.; Moon, H.J.; You, B.R.; Park, W.H. The attenuation of MG132, a proteasome inhibitor, induced A549 lung cancer cell death by p38 inhibitor in ROS-independent manner. Oncol. Res., 2009, 18(7), 315-322. doi: 10.3727/096504010X12626118079949 PMID: 20377132
  19. Park; Moon, H.J.; You, B.R.; Park, W.H. The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH. Oncol. Rep., 2009, 22(1), 215-221. doi: 10.3892/or_00000427 PMID: 19513526
  20. Matsuo, Y.; Sawai, H.; Ochi, N.; Yasuda, A.; Sakamoto, M.; Takahashi, H.; Funahashi, H.; Takeyama, H.; Guha, S. Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking NF-kappaB activity. Dig. Dis. Sci., 2010, 55(4), 1167-1176. doi: 10.1007/s10620-009-0814-4 PMID: 19399612
  21. Park, W.H.; Kim, S.H. MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol. Rep., 2012, 27(4), 1284-1291. doi: 10.3892/or.2012.1642 PMID: 22266922
  22. Zhu, W.; Liu, J.; Nie, J.; Sheng, W.; Cao, H.; Shen, W.; Dong, A.; Zhou, J.; Jiao, Y.; Zhang, S.; Cao, J. MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo. Oncol. Rep., 2015, 34(4), 2083-2089. doi: 10.3892/or.2015.4169 PMID: 26238156
  23. Zhang, Y.; Yang, B.; Zhao, J.; Li, X.; Zhang, L.; Zhai, Z. Proteasome inhibitor carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) enhances therapeutic effect of paclitaxel on breast cancer by inhibiting nuclear factor (NF)-κB signaling. Med. Sci. Monit., 2018, 24, 294-304. doi: 10.12659/MSM.908139 PMID: 29332931
  24. Chen, J.J.; Huang, W.C.; Chen, C.C. Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein. Mol. Biol. Cell, 2005, 16(12), 5579-5591. doi: 10.1091/mbc.e05-08-0778 PMID: 16195339
  25. Chen, H.; Ren, X.; Wang, W.; Zhang, Y.; Chen, S.; Zhang, B.; Wang, L. Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells. Biomed. Pharmacother., 2014, 68(6), 709-713. doi: 10.1016/j.biopha.2014.07.011 PMID: 25092240
  26. Tsakiri, E.N.; Trougakos, I.P. The amazing ubiquitin-proteasome system: structural components and implication in aging. Int. Rev. Cell Mol. Biol., 2015, 314, 171-237. doi: 10.1016/bs.ircmb.2014.09.002 PMID: 25619718
  27. Kurozumi, N.; Tsujioka, T.; Ouchida, M.; Sakakibara, K.; Nakahara, T.; Suemori, S.; Takeuchi, M.; Kitanaka, A.; Shibakura, M.; Tohyama, K. VLX1570 induces apoptosis through the generation of ROS and induction of ER stress on leukemia cell lines. Cancer Sci., 2021, 112(8), 3302-3313. doi: 10.1111/cas.14982 PMID: 34032336
  28. Zhang, W.; Che, Q.; Tan, H.; Qi, X.; Li, J.; Li, D.; Gu, Q.; Zhu, T.; Liu, M. Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system. Sci. Rep., 2017, 7(1), 42180. doi: 10.1038/srep42180 PMID: 28176847
  29. Gadhave, K.; Kumar, P.; Kapuganti, S.; Uversky, V.; Giri, R. Unstructured biology of proteins from ubiquitin-proteasome system: Roles in cancer and neurodegenerative diseases. Biomolecules, 2020, 10(5), 796. doi: 10.3390/biom10050796 PMID: 32455657
  30. Lipchick, B.C.; Fink, E.E.; Nikiforov, M.A. Oxidative stress and proteasome inhibitors in multiple myeloma. Pharmacol. Res., 2016, 105, 210-215. doi: 10.1016/j.phrs.2016.01.029 PMID: 26827824
  31. Perillo, B.; Di Donato, M.; Pezone, A.; Di Zazzo, E.; Giovannelli, P.; Galasso, G.; Castoria, G.; Migliaccio, A. ROS in cancer therapy: the bright side of the moon. Exp. Mol. Med., 2020, 52(2), 192-203. doi: 10.1038/s12276-020-0384-2 PMID: 32060354
  32. Sahoo, B.M.; Banik, B.K.; Borah, P.; Jain, A. Reactive oxygen species (ROS): Key components in cancer therapies. Anticancer. Agents Med. Chem., 2022, 22(2), 215-222. doi: 10.2174/1871520621666210608095512 PMID: 34102991
  33. Nakamura, H.; Takada, K. Reactive oxygen species in cancer: Current findings and future directions. Cancer Sci., 2021, 112(10), 3945-3952. doi: 10.1111/cas.15068 PMID: 34286881
  34. He, M.; Wang, M.; Xu, T.; Zhang, M.; Dai, H.; Wang, C.; Ding, D.; Zhong, Z. Reactive oxygen species-powered cancer immunotherapy: Current status and challenges. J. Control. Release, 2023, 356, 623-648. doi: 10.1016/j.jconrel.2023.02.040 PMID: 36868519
  35. Siomek, A.; Tujakowski, J.; Gackowski, D.; Rozalski, R.; Foksinski, M.; Dziaman, T.; Roszkowski, K.; Olinski, R. Severe oxidatively damaged DNA after cisplatin treatment of cancer patients. Int. J. Cancer, 2006, 119(9), 2228-2230. doi: 10.1002/ijc.22088 PMID: 16804900
  36. Arihara, Y.; Takada, K.; Kamihara, Y.; Hayasaka, N.; Nakamura, H.; Murase, K.; Ikeda, H.; Iyama, S.; Sato, T.; Miyanishi, K.; Kobune, M.; Kato, J. Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma. Oncotarget, 2017, 8(39), 65889-65899. doi: 10.18632/oncotarget.19508 PMID: 29029480
  37. Nakamura, H.; Takada, K.; Arihara, Y.; Hayasaka, N.; Murase, K.; Iyama, S.; Kobune, M.; Miyanishi, K.; Kato, J. Six-transmembrane epithelial antigen of the prostate 1 protects against increased oxidative stress via a nuclear erythroid 2-related factor pathway in colorectal cancer. Cancer Gene Ther., 2019, 26(9-10), 313-322. doi: 10.1038/s41417-018-0056-8 PMID: 30401882
  38. Srinivas, U.S.; Tan, B.W.Q.; Vellayappan, B.A.; Jeyasekharan, A.D. ROS and the DNA damage response in cancer. Redox Biol., 2019, 25, 101084. doi: 10.1016/j.redox.2018.101084 PMID: 30612957
  39. He, L.; Nan, M.H.; Oh, H.C.; Kim, Y.H.; Jang, J.H.; Erikson, R.L.; Ahn, J.S.; Kim, B.Y. Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells. Biochem. Biophys. Res. Commun., 2011, 409(3), 489-493. doi: 10.1016/j.bbrc.2011.05.032 PMID: 21600879
  40. Paniagua Soriano, G.; De Bruin, G.; Overkleeft, H.S.; Florea, B.I. Toward understanding induction of oxidative stress and apoptosis by proteasome inhibitors. Antioxid. Redox Signal., 2014, 21(17), 2419-2443. doi: 10.1089/ars.2013.5794 PMID: 24437477
  41. Cui, W.; Bai, Y.; Luo, P.; Miao, L.; Cai, L. Preventive and therapeutic effects of MG132 by activating Nrf2-ARE signaling pathway on oxidative stress-induced cardiovascular and renal injury. Oxid. Med. Cell. Longev., 2013, 2013(1), 1-10. doi: 10.1155/2013/306073 PMID: 23533688
  42. Georgiou-Siafis, S.K.; Tsiftsoglou, A.S. Activation of KEAP1/NRF2 stress signaling involved in the molecular basis of hemin-induced cytotoxicity in human pro-erythroid K562 cells. Biochem. Pharmacol., 2020, 175, 113900. doi: 10.1016/j.bcp.2020.113900 PMID: 32156661
  43. Alva, N.; Panisello-Roselló, A.; Flores, M.; Roselló-Catafau, J.; Carbonell, T. Ubiquitin-proteasome system and oxidative stress in liver transplantation. World J. Gastroenterol., 2018, 24(31), 3521-3530. doi: 10.3748/wjg.v24.i31.3521 PMID: 30131658
  44. Park, S.; Park, J.A.; Yoo, H.; Park, H.B.; Lee, Y. Proteasome inhibitor-induced cleavage of HSP90 is mediated by ROS generation and caspase 10-activation in human leukemic cells. Redox Biol., 2017, 13, 470-476. doi: 10.1016/j.redox.2017.07.010 PMID: 28715732
  45. Redza-Dutordoir, M.; Averill-Bates, D.A. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta Mol. Cell Res., 2016, 1863(12), 2977-2992. doi: 10.1016/j.bbamcr.2016.09.012 PMID: 27646922
  46. Kodroń, A.; Mussulini, B.H.; Pilecka, I.; Chacińska, A. The ubiquitin-proteasome system and its crosstalk with mitochondria as therapeutic targets in medicine. Pharmacol. Res., 2021, 163, 105248. doi: 10.1016/j.phrs.2020.105248 PMID: 33065283
  47. Lehmann, G.; Udasin, R.G.; Ciechanover, A. On the linkage between the ubiquitin-proteasome system and the mitochondria. Biochem. Biophys. Res. Commun., 2016, 473(1), 80-86. doi: 10.1016/j.bbrc.2016.03.055 PMID: 26996128
  48. Bragoszewski, P.; Turek, M.; Chacinska, A. Control of mitochondrial biogenesis and function by the ubiquitin–proteasome system. Open Biol., 2017, 7(4), 170007. doi: 10.1098/rsob.170007 PMID: 28446709
  49. Haberecht-Müller, S.; Krüger, E.; Fielitz, J. Out of control: The role of the ubiquitin proteasome system in skeletal muscle during inflammation. Biomolecules, 2021, 11(9), 1327. doi: 10.3390/biom11091327 PMID: 34572540
  50. Cockram, P.E.; Kist, M.; Prakash, S.; Chen, S.H.; Wertz, I.E.; Vucic, D. Ubiquitination in the regulation of inflammatory cell death and cancer. Cell Death Differ., 2021, 28(2), 591-605. doi: 10.1038/s41418-020-00708-5 PMID: 33432113
  51. Ikeda, F. Diverse ubiquitin codes in the regulation of inflammatory signaling. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2020, 96(9), 431-439. doi: 10.2183/pjab.96.032 PMID: 33177297
  52. Çetin, G.; Klafack, S.; Studencka-Turski, M.; Krüger, E.; Ebstein, F. The ubiquitin–proteasome system in immune cells. Biomolecules, 2021, 11(1), 60. doi: 10.3390/biom11010060 PMID: 33466553
  53. Ali, K.; Saleh, Z.; Jalal, J. Effect of local propolis irrigation in experimental periodontitis in rats on inflammatory markers (IL-1β and TNF-α) and oxidative stress. Indian J. Dent. Res., 2020, 31(6), 893-898. doi: 10.4103/ijdr.IJDR_909_19 PMID: 33753660
  54. Roohi, E.; Jaafari, N.; Hashemian, F. On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos? J. Neuroinflammation, 2021, 18(1), 45. doi: 10.1186/s12974-021-02100-7 PMID: 33593388
  55. He, X.; Ma, Q.; Fan, Y.; Zhao, B.; Wang, W.; Zhu, F.; Ma, X.; Zhou, L. The role of cytokines in predicting the efficacy of acute stage treatment in patients with schizophrenia. Neuropsychiatr. Dis. Treat., 2020, 16, 191-199. doi: 10.2147/NDT.S218483 PMID: 32021213
  56. Nur Husna, S.M.; Md Shukri, N.; Mohd Ashari, N.S.; Wong, K.K. IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ, 2022, 10, e13444. doi: 10.7717/peerj.13444 PMID: 35663523
  57. Onuma, K.; Kanda, Y.; Suzuki Ikeda, S.; Sakaki, R.; Nonomura, T.; Kobayashi, M.; Osaki, M.; Shikanai, M.; Kobayashi, H.; Okada, F. Fermented brown rice and rice bran with Aspergillus oryzae (FBRA) prevents inflammation-related carcinogenesis in mice, through inhibition of inflammatory cell infiltration. Nutrients, 2015, 7(12), 10237-10250. doi: 10.3390/nu7125531 PMID: 26670250
  58. Shah, S.C.; Itzkowitz, S.H. Colorectal cancer in inflammatory bowel disease: Mechanisms and management. Gastroenterology, 2022, 162(3), 715-730. doi: 10.1053/j.gastro.2021.10.035
  59. Refolo, M.G.; Messa, C.; Guerra, V.; Carr, B.I.; D’Alessandro, R. Inflammatory mechanisms of HCC development. Cancers (Basel), 2020, 12(3), 641. doi: 10.3390/cancers12030641 PMID: 32164265
  60. Lai, H.; Liu, Y.; Wu, J.; Cai, J.; Jie, H.; Xu, Y.; Deng, S. Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics. Front. Pharmacol., 2022, 13, 1078766. doi: 10.3389/fphar.2022.1078766 PMID: 36545311
  61. Liggett, J.L.; Zhang, X.; Eling, T.E.; Baek, S.J. Anti-tumor activity of non-steroidal anti-inflammatory drugs: Cyclooxygenase-independent targets. Cancer Lett., 2014, 346(2), 217-224. doi: 10.1016/j.canlet.2014.01.021 PMID: 24486220
  62. Hajdu, S.I. Pathfinders in oncology from the beginning of the 19th century to the inauguration of the first cancer hospital in the United States. Cancer, 2018, 124(2), 230-241. doi: 10.1002/cncr.31135 PMID: 29149477
  63. David, H. Rudolf Virchow and modern aspects of tumor pathology. Pathol. Res. Pract., 1988, 183(3), 356-364. doi: 10.1016/S0344-0338(88)80138-9 PMID: 3047716
  64. Denk, D.; Greten, F.R. Inflammation: the incubator of the tumor microenvironment. Trends Cancer, 2022, 8(11), 901-914. doi: 10.1016/j.trecan.2022.07.002 PMID: 35907753
  65. Michels, N.; van Aart, C.; Morisse, J.; Mullee, A.; Huybrechts, I. Chronic inflammation towards cancer incidence: A systematic review and meta-analysis of epidemiological studies. Crit. Rev. Oncol. Hematol., 2021, 157, 103177. doi: 10.1016/j.critrevonc.2020.103177 PMID: 33264718
  66. Tan, Z.; Xue, H.; Sun, Y.; Zhang, C.; Song, Y.; Qi, Y. The role of tumor inflammatory microenvironment in lung cancer. Front. Pharmacol., 2021, 12, 688625. doi: 10.3389/fphar.2021.688625 PMID: 34079469
  67. Hibino, S.; Kawazoe, T.; Kasahara, H.; Itoh, S.; Ishimoto, T.; Sakata-Yanagimoto, M.; Taniguchi, K. Inflammation-induced tumorigenesis and metastasis. Int. J. Mol. Sci., 2021, 22(11), 5421. doi: 10.3390/ijms22115421 PMID: 34063828
  68. Zhao, H.; Wu, L.; Yan, G.; Chen, Y.; Zhou, M.; Wu, Y.; Li, Y. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct. Target. Ther., 2021, 6(1), 263. doi: 10.1038/s41392-021-00658-5 PMID: 34248142
  69. Liu, X.; Yin, L.; Shen, S.; Hou, Y. Inflammation and cancer: paradoxical roles in tumorigenesis and implications in immunotherapies. Genes Dis., 2023, 10(1), 151-164. doi: 10.1016/j.gendis.2021.09.006 PMID: 37013041
  70. Piotrowski, I.; Kulcenty, K.; Suchorska, W. Interplay between inflammation and cancer. Rep. Pract. Oncol. Radiother., 2020, 25(3), 422-427. doi: 10.1016/j.rpor.2020.04.004 PMID: 32372882
  71. Korniluk, A.; Koper, O.; Kemona, H.; Dymicka-Piekarska, V. From inflammation to cancer. Ir J Med Sci., 2017, 186(1), 57-62. doi: 10.1007/s11845-016-1464-0
  72. Rudmann, D.G. On-target and off-target-based toxicologic effects. Toxicol. Pathol., 2013, 41(2), 310-314. doi: 10.1177/0192623312464311 PMID: 23085982
  73. Lin, A.; Giuliano, C.J.; Palladino, A.; John, K.M.; Abramowicz, C.; Yuan, M.L.; Sausville, E.L.; Lukow, D.A.; Liu, L.; Chait, A.R.; Galluzzo, Z.C.; Tucker, C.; Sheltzer, J.M. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med., 2019, 11(509), eaaw8412. doi: 10.1126/scitranslmed.aaw8412 PMID: 31511426
  74. Ma, N.; Chen, X.; Johnston, L.J.; Ma, X. Gut microbiota‐stem cell niche crosstalk: A new territory for maintaining intestinal homeostasis. iMeta, 2022, 1(4), e54. doi: 10.1002/imt2.54 PMID: 38867904
  75. Strikoudis, A.; Guillamot, M.; Aifantis, I. Regulation of stem cell function by protein ubiquitylation. EMBO Rep., 2014, 15(4), 365-382. doi: 10.1002/embr.201338373 PMID: 24652853
  76. Rodriguez-Fernandez, I.A.; Qi, Y.; Jasper, H. Loss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction. Nat. Commun., 2019, 10(1), 1050. doi: 10.1038/s41467-019-08982-9 PMID: 30837466

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Bentham Science Publishers, 2025