Year 2025,
Volume: 15 Issue: 4, 313 - 319
Ertan Katırcı
,
Remziye Kendirci
,
Suna Karadeniz Saygılı
,
Nureddin Cengiz
References
-
Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. Feb 1 2022;95(1130):20211033. doi:10.1259/bjr.20211033
-
Dunne M, Dou YN, Drake DM, et al. Hyperthermia-mediated drug delivery induces biological effects at the tumor and molecular levels that improve cisplatin efficacy in triple negative breast cancer. J Control Release. Jul 28 2018;282:35-45. doi:10.1016/j.jconrel.2018.04.029
-
Kenny PA, Lee GY, Myers CA, et al. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol Oncol. Jun 2007;1(1):84-96. doi:10.1016/j.molonc.2007.02.004
-
Guerrab AE, Bamdad M, Bignon YJ, Penault‐Llorca F, Aubel C. Co-Targeting EGFR and mTOR with gefitinib and everolimus in triple-negative breast cancer cells. Scientific Reports. 2020;10(1). doi:10.1038/s41598-020-63310-2
-
Cai WL, Chen JF-Y, Chen H, et al. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. Elife. 2022;11. doi:10.7554/elife.78163
-
Vora H, Rajvik KN, Patel N. Clinical utility of predictive markers in triple negative breast cancer. International Journal of Research and Review. 2022;9(12):179-186. doi:10.52403/ijrr.20221219
-
Ma J, Dong C, Cao Y, Ma B. Dual Target of EGFR and mTOR suppresses triple-negative breast cancer cell growth by regulating the phosphorylation of mTOR downstream proteins. Breast Cancer Targets and Therapy. 2023;Volume 15:11-24. doi:10.2147/bctt.s390017
-
Wen W, Marcinkowski E, Luyimbazi D, et al. Eribulin synergistically increases anti-tumor activity of an mTOR inhibitor by inhibiting pAKT/pS6K/pS6 in triple negative breast cancer. Cells. 2019;8(9):1010. doi:10.3390/cells8091010
-
Dai L, Wang L, Tan C, et al. Sophoridine derivatives induce apoptosis and autophagy to suppress the growth of triple‐negative breast cancer through inhibition of mTOR signaling. Chemmedchem. 2021;17(1). doi:10.1002/cmdc.202100434
Yao C, Liu J, Shao L. Rapamycin inhibits the proliferation and apoptosis of gastric cancer cells by down regulating the expression of survivin. Hepatogastroenterology. May-Jun 2011;58(107-108):1075-80.
-
He J, McLaughlin RP, Noord VEvd, et al. Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer. Breast Cancer Research and Treatment. 2019;178(2):263-274. doi:10.1007/s10549-019-05380-z
-
Guo Y, Pei X. Tetrandrine-induced autophagy in MDA-MB-231 triple-negative breast cancer cell through the inhibition of PI3K/AKT/mTOR signaling. Evidence-Based Complementary and Alternative Medicine. 2019;2019:1-11. doi:10.1155/2019/7517431
-
Basho R, Yam C, Gilcrease MZ, et al. Comparative effectiveness of an mTOR-based systemic therapy regimen in advanced, metaplastic and nonmetaplastic triple-negative breast cancer. The Oncologist. 2018;23(11):1300-1309. doi:10.1634/theoncologist.2017-0498
-
Cheng SH, Tseng YM, Wu SH, Tsai SM, Tsai LY. Whey protein concentrate renders MDA-MB-231 cells sensitive to rapamycin by altering cellular redox state and activating GSK3β/mTOR signaling. Sci Rep. Nov 21 2017;7(1):15976. doi:10.1038/s41598-017-14159-5
-
Cuesta R, Holz MK. RSK-mediated down-regulation of PDCD4 is required for proliferation, survival, and migration in a model of triple-negative breast cancer. Oncotarget. May 10 2016;7(19):27567-83. doi:10.18632/oncotarget.8375
-
Hallare AV, Köhler HR, Triebskorn R. Developmental toxicity and stress protein responses in zebrafish embryos after exposure to diclofenac and its solvent, DMSO. Chemosphere. Aug 2004;56(7):659-66. doi:10.1016/j.chemosphere.2004.04.007
-
Gurtovenko AA, Anwar J. Modulating the structure and properties of cell membranes: The molecular mechanism of action of dimethyl sulfoxide. J Phys Chem B. Sep 6 2007;111(35):10453-60. doi:10.1021/jp073113e
-
Ramírez-Coronel AA, Rostami A, Younus LA, et al. Designing effective multi-target drugs and identifying biomarkers in Recurrent Pregnancy Loss (RPL) using in vivo, in vitro, and in silico approaches. Biomedicines. Mar 13 2023;11(3). doi:10.3390/biomedicines11030879
-
Segatto I, Berton S, Sonego M, et al. p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation. Mol Oncol. May 2014;8(3):766-80. doi:10.1016/j.molonc.2014.02.006
-
Liang C-C, Park AY, Guan J-L. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nature Protocols. February 01 2007;2(2):329-333. doi:10.1038/nprot.2007.30
-
Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N. Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta. Mar 2010;1804(3):433-9. doi:10.1016/j.bbapap.2009.12.001
-
Jacquier M, Kuriakose S, Bhardwaj A, et al. Investigation of novel regulation of N-myristoyltransferase by mammalian target of rapamycin in breast cancer cells. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-30447-0
-
Zhang F, Cheng T, Zhang S-X. Mechanistic target of rapamycin (mTOR): A potential new therapeutic target for rheumatoid arthritis. Arthritis Research & Therapy. February 2023;25. doi:10.1186/s13075-023-03181-w
-
Artemenko M, Zhong SSW, To SKY, Wong AST. p70 S6 kinase as a therapeutic target in cancers: More than just an mTOR effector. Cancer Letters. 2022;535:215593. doi:10.1016/j.canlet.2022.215593
-
Zhang H, Hu J, Fu R, et al. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-29308-7
-
Bouyahya A, El Allam A, Aboulaghras S, et al. Targeting mTOR as a cancer therapy: Recent advances in natural bioactive compounds and immunotherapy. Cancers (Basel). Nov 10 2022;14(22). doi:10.3390/cancers14225520
Migration Suppressive Effect of Rapamycin in MDA-MB-231 Cells
Year 2025,
Volume: 15 Issue: 4, 313 - 319
Ertan Katırcı
,
Remziye Kendirci
,
Suna Karadeniz Saygılı
,
Nureddin Cengiz
Abstract
Objective: The current study aims to evaluate the effects of rapamycin, an mTOR inhibitor, on cell migration and cell proliferation in the MDA-MB-231 human breast cancer cell line, which is a triple-negative breast cancer (TNBC) model. TNBC is notable for its aggressive phenotype and lack of any useful conventional treatment methods, and due to this tumor progression, it's necessary to look at new treatment methods.
Materials and Methods: The study utilized a wound healing assay to assess the impact of rapamycin on cell migration, and Western blot analysis was performed to examine the inhibition of mTOR signaling.
Results: The findings indicated that rapamycin inhibited cell migration and proliferation due to selective inhibition of mTOR and p70S6K phosphorylation, which are two of the principal proteins implicated in tumor progression. Of note, rapamycin administration did not affect total protein levels for these proteins, which indicates that rapamycin has an agonistic effect on mTOR and p70S6K.
Conclusion: These findings suggest that rapamycin may serve as a potential therapeutic agent for controlling tumor growth and metastasis in TNBC. Further studies still need to be performed to determine the clinical efficacy of this treatment in vivo.
References
-
Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. Feb 1 2022;95(1130):20211033. doi:10.1259/bjr.20211033
-
Dunne M, Dou YN, Drake DM, et al. Hyperthermia-mediated drug delivery induces biological effects at the tumor and molecular levels that improve cisplatin efficacy in triple negative breast cancer. J Control Release. Jul 28 2018;282:35-45. doi:10.1016/j.jconrel.2018.04.029
-
Kenny PA, Lee GY, Myers CA, et al. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol Oncol. Jun 2007;1(1):84-96. doi:10.1016/j.molonc.2007.02.004
-
Guerrab AE, Bamdad M, Bignon YJ, Penault‐Llorca F, Aubel C. Co-Targeting EGFR and mTOR with gefitinib and everolimus in triple-negative breast cancer cells. Scientific Reports. 2020;10(1). doi:10.1038/s41598-020-63310-2
-
Cai WL, Chen JF-Y, Chen H, et al. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. Elife. 2022;11. doi:10.7554/elife.78163
-
Vora H, Rajvik KN, Patel N. Clinical utility of predictive markers in triple negative breast cancer. International Journal of Research and Review. 2022;9(12):179-186. doi:10.52403/ijrr.20221219
-
Ma J, Dong C, Cao Y, Ma B. Dual Target of EGFR and mTOR suppresses triple-negative breast cancer cell growth by regulating the phosphorylation of mTOR downstream proteins. Breast Cancer Targets and Therapy. 2023;Volume 15:11-24. doi:10.2147/bctt.s390017
-
Wen W, Marcinkowski E, Luyimbazi D, et al. Eribulin synergistically increases anti-tumor activity of an mTOR inhibitor by inhibiting pAKT/pS6K/pS6 in triple negative breast cancer. Cells. 2019;8(9):1010. doi:10.3390/cells8091010
-
Dai L, Wang L, Tan C, et al. Sophoridine derivatives induce apoptosis and autophagy to suppress the growth of triple‐negative breast cancer through inhibition of mTOR signaling. Chemmedchem. 2021;17(1). doi:10.1002/cmdc.202100434
Yao C, Liu J, Shao L. Rapamycin inhibits the proliferation and apoptosis of gastric cancer cells by down regulating the expression of survivin. Hepatogastroenterology. May-Jun 2011;58(107-108):1075-80.
-
He J, McLaughlin RP, Noord VEvd, et al. Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer. Breast Cancer Research and Treatment. 2019;178(2):263-274. doi:10.1007/s10549-019-05380-z
-
Guo Y, Pei X. Tetrandrine-induced autophagy in MDA-MB-231 triple-negative breast cancer cell through the inhibition of PI3K/AKT/mTOR signaling. Evidence-Based Complementary and Alternative Medicine. 2019;2019:1-11. doi:10.1155/2019/7517431
-
Basho R, Yam C, Gilcrease MZ, et al. Comparative effectiveness of an mTOR-based systemic therapy regimen in advanced, metaplastic and nonmetaplastic triple-negative breast cancer. The Oncologist. 2018;23(11):1300-1309. doi:10.1634/theoncologist.2017-0498
-
Cheng SH, Tseng YM, Wu SH, Tsai SM, Tsai LY. Whey protein concentrate renders MDA-MB-231 cells sensitive to rapamycin by altering cellular redox state and activating GSK3β/mTOR signaling. Sci Rep. Nov 21 2017;7(1):15976. doi:10.1038/s41598-017-14159-5
-
Cuesta R, Holz MK. RSK-mediated down-regulation of PDCD4 is required for proliferation, survival, and migration in a model of triple-negative breast cancer. Oncotarget. May 10 2016;7(19):27567-83. doi:10.18632/oncotarget.8375
-
Hallare AV, Köhler HR, Triebskorn R. Developmental toxicity and stress protein responses in zebrafish embryos after exposure to diclofenac and its solvent, DMSO. Chemosphere. Aug 2004;56(7):659-66. doi:10.1016/j.chemosphere.2004.04.007
-
Gurtovenko AA, Anwar J. Modulating the structure and properties of cell membranes: The molecular mechanism of action of dimethyl sulfoxide. J Phys Chem B. Sep 6 2007;111(35):10453-60. doi:10.1021/jp073113e
-
Ramírez-Coronel AA, Rostami A, Younus LA, et al. Designing effective multi-target drugs and identifying biomarkers in Recurrent Pregnancy Loss (RPL) using in vivo, in vitro, and in silico approaches. Biomedicines. Mar 13 2023;11(3). doi:10.3390/biomedicines11030879
-
Segatto I, Berton S, Sonego M, et al. p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation. Mol Oncol. May 2014;8(3):766-80. doi:10.1016/j.molonc.2014.02.006
-
Liang C-C, Park AY, Guan J-L. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nature Protocols. February 01 2007;2(2):329-333. doi:10.1038/nprot.2007.30
-
Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N. Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta. Mar 2010;1804(3):433-9. doi:10.1016/j.bbapap.2009.12.001
-
Jacquier M, Kuriakose S, Bhardwaj A, et al. Investigation of novel regulation of N-myristoyltransferase by mammalian target of rapamycin in breast cancer cells. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-30447-0
-
Zhang F, Cheng T, Zhang S-X. Mechanistic target of rapamycin (mTOR): A potential new therapeutic target for rheumatoid arthritis. Arthritis Research & Therapy. February 2023;25. doi:10.1186/s13075-023-03181-w
-
Artemenko M, Zhong SSW, To SKY, Wong AST. p70 S6 kinase as a therapeutic target in cancers: More than just an mTOR effector. Cancer Letters. 2022;535:215593. doi:10.1016/j.canlet.2022.215593
-
Zhang H, Hu J, Fu R, et al. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-29308-7
-
Bouyahya A, El Allam A, Aboulaghras S, et al. Targeting mTOR as a cancer therapy: Recent advances in natural bioactive compounds and immunotherapy. Cancers (Basel). Nov 10 2022;14(22). doi:10.3390/cancers14225520