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Rapamycin Enhanced Sensitivity of HT-29 Cells to 5-Fluororacil by Promoting Autophagy

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We studied the effect of cytostatic rapamycin on the antitumor activity of 5-fluorouracil (5-FU). To this end, HT-29 cells were treated with 5-FU, or rapamycin, or their combination. The proliferation and apoptosis of treated cells were evaluated using Cell Counting Kit-8 kit and flow cytometry, respectively. The autophagy was evaluated by transmission electron microscopy and Western blotting by the expression of p62, LC3I, and LC3II proteins. 5-FU inhibited proliferation and promoted apoptosis of HT-29 cells, and the combination of 5-FU with rapamycin potentiated both effects. Rapamycin promoted accumulation of autophagosome/autolysosome and enhanced the level of LC3II/LC3I. Thus, rapamycin enhances the antitumor activity of 5-FU by stimulating autophagy and increasing LC3II/LC3I. The results confirm a potential therapeutic strategy for the clinical application of 5-FU.

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References

  1. Blagosklonny MV. Rapamycin for longevity: opinion article. Aging (Albany NY). 2019;11(19):8048-8067. https://doi.org/10.18632/aging.102355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen J, Lu H, Yan D, Cui F, Wang X, Yu F, Xue Y, Feng X, Wang J, Wang X, Jiang T, Zhang M, Zhao S, Yu Y, Tang H, Peng Z. PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy. Oncotarget. 2015;6(1):355-67. https://doi.org/10.18632/oncotarget.2803

    Article  PubMed  Google Scholar 

  3. Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, Xiao B, Worley PF, Powell JD. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 2011;12(4):295-303. https://doi.org/10.1038/ni.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. He XX, Huang CK, Xie BS. Autophagy inhibition enhanced 5-FU-induced cell death in human gastric carcinoma BGC-823 cells. Mol. Med. Rep. 2018;17(5):6768-6776. https://doi.org/10.3892/mmr.2018.8661

    Article  CAS  PubMed  Google Scholar 

  5. Liu C, Liu L, Zhu HD, Sheng JQ, Wu XL, He XX, Tian DA, Liao JZ, Li PY. Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux. Sci. Rep. 2018;8(1):4108. https://doi.org/10.1038/s41598-018-22339-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sato M, Seki T, Konno A, Hirai H, Kurauchi Y, Hisatsune A, Katsuki H. Rapamycin activates mammalian microautophagy. J. Pharmacol. Sci. 2019;140(2):201-204. https://doi.org/10.1016/j.jphs.2019.05.007

    Article  CAS  PubMed  Google Scholar 

  7. Svatek RS, Ji N, de Leon E, Mukherjee NZ, Kabra A, Hurez V, Nicolas M, Michalek JE, Javors M, Wheeler K, Sharp ZD, Livi CB, Shu ZJ, Henkes D, Curiel TJ. Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer. Cancer Immunol. Res. 2019;7(3):466-475. https://doi.org/10.1158/2326-6066.CIR-18-0336

    Article  CAS  PubMed  Google Scholar 

  8. Tanida I, Ueno T, Kominami E. LC3 and Autophagy. Methods Mol. Biol. 2008;445:77-88. https://doi.org/10.1007/978-1-59745-157-4_4

    Article  CAS  PubMed  Google Scholar 

  9. Wang M, Han D, Yuan Z, Hu H, Zhao Z, Yang R, Jin Y, Zou C, Chen Y, Wang G, Gao X, Wang X. Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy. Cell Death Dis. 2018;9(12):1149. https://doi.org/10.1038/s41419-018-1187-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang Y, Zhang H. Regulation of Autophagy by mTOR Signaling Pathway. Adv. Exp. Med. Biol. 2019;1206:67-83. https://doi.org/10.1007/978-981-15-0602-4_

    Article  CAS  PubMed  Google Scholar 

  11. Wei Y, Yang P, Cao S, Zhao L. The combination of curcumin and 5-fluorouracil in cancer therapy. Arch. Pharm. Res. 2018;41(1):1-13. https://doi.org/10.1007/s12272-017-0979-x

    Article  CAS  PubMed  Google Scholar 

  12. White E, Mehnert JM, Chan CS. Autophagy, Metabolism, and Cancer. Clin. Cancer Res. 2015;21(22):5037-5046. https://doi.org/10.1158/1078-0432.CCR-15-0490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xu M, Bu LM, Wu K, Lu LG, Wang XP. Rapamycin inhibits the proliferation of SW1990 pancreatic cancer cell. Eur. Rev. Med. Pharmacol. Sci. 2015;19(16):3072-3079.

    CAS  PubMed  Google Scholar 

  14. Yang D, Qu J, Qu X, Cao Y, Xu L, Hou K, Feng W, Liu Y. Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells // Cancer Chemother. Pharmacol. 2015;76(3):575-586. https://doi.org/10.1007/s00280-015-2749-0

    Article  CAS  Google Scholar 

  15. Zhang S, Zheng F, Zhang L, Huang Z, Huang X, Pan Z, Chen S, Xu C, Jiang Y, Gu S, Zhao C, Zhang Q, Shi G. LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells. J. Exp. Clin. Cancer Res. 2020;39(1):131. https://doi.org/10.1186/s13046-020-01610-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Abdominal Radiation Oncology Ward 2, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    S. Chen

  2. Department of Oncology, Dongying People’s Hospital, Dongying, Shandong, China

    S. Chen, J. Yang, F. Wang, X. Gao, Qiang Liu & Qian Liu

  3. Department of Abdominal Radiation Oncology Ward 2, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Y. Zhang & Y. Yu

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  1. S. Chen
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Correspondence to Y. Yu.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 173, No. 4, pp. 456-461, April, 2022

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Chen, S., Yang, J., Wang, F. et al. Rapamycin Enhanced Sensitivity of HT-29 Cells to 5-Fluororacil by Promoting Autophagy. Bull Exp Biol Med 173, 448–453 (2022). https://doi.org/10.1007/s10517-022-05585-1

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  • DOI: https://doi.org/10.1007/s10517-022-05585-1

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