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Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Research Article

Expression of mTOR/70S6K Signaling Pathway in Melanoma Cancer Cells and the Effects of Dacarbazine and Metformin

Author(s): Marjan Hajimoradi Javarsiani*, Shagayegh Haghjooy Javanmard and Javad Sajedianfard

Volume 18, Issue 2, 2022

Published on: 30 November, 2021

Page: [118 - 122] Pages: 5

DOI: 10.2174/1573394717666210922151736

Price: $65

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Abstract

Background: Melanoma, also known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin but may rarely occur in the mouth, intestines or, eye. This study aims to examine the expression of the mammalian target of rapamycin (mTOR)/70S6K signaling pathway in melanoma cancer.

Methods: The B16F10 cell line treated with dacarbazine IC50 and different concentrations of metformin (0.5, 2, and 8 mM) for 24 hr and mTOR and 70S6k proteins expression were examined by western blotting. Cell viability was measured by MTT assay.

Results: Western blot analysis showed that after different concentrations of metformin and dacarbazine treatments, the mTOR and 70S6K protein expression significantly (P<0.05) decreased.

Conclusion: Metformin-induced repression of mTOR/70S6k axis activity disrupts B16F10 growth. Thus, we believe that combination therapy may be a suitable potential therapeutic target for melanoma cancer.

Keywords: mTOR, 70S6k, cancer, melanoma, therapy, MTT assay.

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[1]
Polsky D, Cordon-Cardo C. Oncogenes in melanoma. Oncogene 2003; 22(20): 3087-91.
[http://dx.doi.org/10.1038/sj.onc.1206449] [PMID: 12789285]
[2]
Diffey BL. Solar ultraviolet radiation effects on biological systems. Phys Med Biol 1991; 36(3): 299-328.
[http://dx.doi.org/10.1088/0031-9155/36/3/001] [PMID: 1645473]
[3]
Abeyama K, Eng W, Jester JV, et al. A role for NF-kappaB-dependent gene transactivation in sunburn. J Clin Invest 2000; 105(12): 1751-9.
[http://dx.doi.org/10.1172/JCI9745] [PMID: 10862790]
[4]
Leo MS, Sivamani RK. Phytochemical modulation of the Akt/mTOR pathway and its potential use in cutaneous disease. Arch Dermatol Res 2014; 306(10): 861-71.
[http://dx.doi.org/10.1007/s00403-014-1480-8] [PMID: 24972910]
[5]
Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18(16): 1926-45.
[http://dx.doi.org/10.1101/gad.1212704] [PMID: 15314020]
[6]
Janus A, Robak T, Smolewski P. The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and targeted antitumour therapy. Cell Mol Biol Lett 2005; 10(3): 479-98.
[PMID: 16217558]
[7]
El-Arabey AA. New insight for metformin against bladder cancer. Genes Environ 2017; 39: 13.
[http://dx.doi.org/10.1186/s41021-017-0074-z] [PMID: 28373897]
[8]
Hajimoradi J M, Sajedianfard J, Haghjooy J S. The effects of metformin on the hippo pathway in the proliferation of melanoma cancer cells: a preclinical study. Arch Physiol Biochem 2020; 1-6.
[http://dx.doi.org/10.1080/13813455.2020.1760304] [PMID: 32407182]
[9]
Chang HH, Moro A, Chou CEN, et al. Metformin decreases the incidence of pancreatic ductal adenocarcinoma promoted by diet-induced obesity in the conditional KrasG12D mouse model. Sci Rep 2018; 8(1): 5899.
[http://dx.doi.org/10.1038/s41598-018-24337-8] [PMID: 29651002]
[10]
Ismail H. F, Didari T, Khan F, Niaz K, Mojtahedzadeh M, Abdollahi M. A review on the protective effects of metformin in sepsis-induced organ failure. Cell J 2020; 21(4): 363-70.
[PMID: 31376317]
[11]
Gonzalez-Angulo AM, Meric-Bernstam F. Metformin: a therapeutic opportunity in breast cancer. Clin Cancer Res 2010; 16(6): 1695-700.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1805] [PMID: 20215559]
[12]
Ben S I, Laurent K, Giuliano S, et al. Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Cancer Res 2010; 70(6): 2465-75.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2782] [PMID: 20215500]
[13]
Steinberg GR, Carling D. AMP-activated protein kinase: the current landscape for drug development. Nat Rev Drug Discov 2019; 18(7): 527-51.
[http://dx.doi.org/10.1038/s41573-019-0019-2] [PMID: 30867601]
[14]
Chamcheu JC, Roy T, Uddin MB, et al. Role and therapeutic targeting of the PI3K/Akt/mTOR signaling pathway in skin cancer: A review of current status and future trends on natural and synthetic agents therapy. Cells 2019; 8(8): 803.
[15]
Alalem M, Ray A, Ray BK. Metformin induces degradation of mTOR protein in breast cancer cells. Cancer Med 2016; 5(11): 3194-204.
[http://dx.doi.org/10.1002/cam4.896] [PMID: 27748082]

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