Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway Corrigendum in /10.3892/etm.2022.11372

Liu,Yingshan; Zhang,Yan; Jia,Kun; Dong,Yuhao; Ma,Weiyuan

doi:10.3892/etm.2015.2220

April-2015 Volume 9 Issue 4

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April-2015 Volume 9 Issue 4

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Article

Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway

Corrigendum in: /10.3892/etm.2022.11372

Authors:
- Yingshan Liu
- Yan Zhang
- Kun Jia
- Yuhao Dong
- Weiyuan Ma
View Affiliations / Copyright

Affiliations: School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Pages: 1401-1406
|
Published online on: January 27, 2015

https://doi.org/10.3892/etm.2015.2220
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Abstract

The ability of metformin, an antidiabetic drug with wide applications, to inhibit tumor cell growth has recently been discovered. The PI3K/Akt signaling pathway has been found to play an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore the effect of metformin on the proliferation of A431 human squamous cell carcinoma cells and the underlying molecular mechanisms. A431 cells in the logarithmic growth phase were treated with 0, 15, 30, 45 and 60 mM metformin for 12, 24 and 36 h, respectively. Cell morphology with 45 mM metformin treatment for 24 h was observed under a microscope. The proliferation of A431 cells was detected by the Cell Counting kit-8 colorimetric method. The mRNA expression levels of PI3K and Akt were detected by reverse transcription‑polymerase chain reaction (RT‑PCR). The protein expression levels of PI3K, Akt and phosphorylated (p)‑Akt were detected by western blot analysis. Metformin treatment caused morphological change in A431 cells and inhibited their proliferation in a significant time‑ and dose‑dependent manner. RT‑PCR results showed that the mRNA expression of PI3K was inhibited by metformin in a time‑ and dose‑dependent manner (P<0.05). However, there was no significant change in the mRNA expression of Akt following metformin treatment (P>0.05). Western blotting results showed that the protein expression levels of PI3K and p‑Akt were inhibited by metformin in a time‑ and dose‑dependent manner (P<0.05). In conclusion, metformin significantly inhibited the proliferation of A431 cells in the current study, which may be strongly associated with the inhibition of the PI3K/Akt signaling pathway.

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1	Samarasinghe V, Madan V and Lear JT: Management of high-risk squamous cell carcinoma of the skin. Expert Rev Anticancer Ther. 11:763–769. 2011. View Article : Google Scholar : PubMed/NCBI
2	Macbeth AE, Grindlay DJ and Williams HC: What’s new in skin cancer? An analysis of guidelines and systematic reviews published in 2008–2009. Clin Exp Dermatol. 36:453–458. 2011. View Article : Google Scholar : PubMed/NCBI
3	van der Geer S, Siemerink M, Reijers HA, Verhaegh ME, Ostertag JU, Neumann HA and Krekels GA: The incidence of skin cancer in dermatology. Clin Exp Dermatol. 38:724–729. 2013.PubMed/NCBI
4	Nguyen TH and Ho DQ: Nonmelanoma skin cancer. Curr Treat Options Oncol. 3:193–203. 2002. View Article : Google Scholar : PubMed/NCBI
5	Samarasinghe V and Madan V: Nonmelanoma skin cancer. J Cutan Aesthet Surg. 5:3–10. 2012. View Article : Google Scholar : PubMed/NCBI
6	American Diabetes Association. Standards of medical care in diabetes - 2013. Diabetes Care. 36(Suppl 1): S11–S66. 2013. View Article : Google Scholar
7	Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR and Morris AD: Metformin and reduced risk of cancer in diabetic patients. BMJ. 330:1304–1305. 2005. View Article : Google Scholar : PubMed/NCBI
8	Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B and Gandini S: Metformin and cancer risk in diabetic patients: A systematic review and meta-analysis. Cancer Prev Res (Phila). 3:1451–1461. 2010. View Article : Google Scholar
9	Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA and Morgan CL: Mortality after incident cancer in people with and without type 2 diabetes: Impact of metformin on survival. Diabetes Care. 35:299–304. 2012. View Article : Google Scholar : PubMed/NCBI
10	Singh S, Singh H, Singh PP, Murad MH and Limburg PJ: Antidiabetic medications and the risk of colorectal cancer in patients with diabetes mellitus: A systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 22:2258–2268. 2013. View Article : Google Scholar : PubMed/NCBI
11	Gallagher EJ and LeRoith D: Diabetes, antihyperglycemic medications and cancer risk: Smoke or fire. Curr Opin Endocrinol Diabetes Obes. 20:485–494. 2013. View Article : Google Scholar : PubMed/NCBI
12	Wright JL and Stanford JL: Metformin use and prostate cancer in Caucasian men: Results from a population-based case-control study. Cancer Causes Control. 20:1617–1622. 2009. View Article : Google Scholar : PubMed/NCBI
13	Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y and Bost F: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 27:3576–3586. 2008. View Article : Google Scholar : PubMed/NCBI
14	Zakikhani M, Dowling R, Fantus IG, Sonenberg N and Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66:10269–10273. 2006. View Article : Google Scholar : PubMed/NCBI
15	Yung MM, Chan DW, et al: Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade. BMC Cancer. 13:3272013. View Article : Google Scholar : PubMed/NCBI
16	Rattan R, Giri S, Hartmann LC and Shridhar V: Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner. J Cell Mol Med. 15:166–178. 2011. View Article : Google Scholar
17	Manning BD and Cantley LC: AKT/PKB signaling: Navigating downstream. Cell. 129:1261–1274. 2007. View Article : Google Scholar : PubMed/NCBI
18	Vivanco I and Sawyers CL: The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2:489–501. 2002. View Article : Google Scholar : PubMed/NCBI
19	Zhou G, Myers R, Li Y, et al: Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 108:1167–1174. 2001. View Article : Google Scholar : PubMed/NCBI
20	Bodmer M, Meier C, Krähenbühl S, Jick SS and Meier CR: Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 33:1304–1308. 2010. View Article : Google Scholar : PubMed/NCBI
21	Byekova YA, Herrmann JL, Xu J, Elmets CA and Athar M: Liver kinase B1 (LKB1) in the pathogenesis of UVB-induced murine basal cell carcinoma. Arch Biochem Biophys. 508:204–211. 2011. View Article : Google Scholar : PubMed/NCBI
22	Karnevi E, Said K, Andersson R and Rosendahl AH: Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. BMC Cancer. 13:2352013. View Article : Google Scholar : PubMed/NCBI
23	Wei W, Jin J, Schlisio S, Harper JW and Kaelin WG Jr: The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell. 8:25–33. 2005. View Article : Google Scholar : PubMed/NCBI
24	Welcker M, Singer J, Loeb KR, Grim J, Bloecher A, Gurien-West M, Clurman BE and Roberts JM: Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell. 12:381–392. 2003. View Article : Google Scholar : PubMed/NCBI
25	Mamane Y, Petroulakis E, Rong L, Yoshida K, Ler LW and Sonenberg N: eIF4E - from translation to transformation. Oncogene. 23:3172–3179. 2004. View Article : Google Scholar : PubMed/NCBI
26	King FW, Skeen J, Hay N and Shtivelman E: Inhibition of Chk1 by activated PKB/Akt. Cell Cycle. 3:634–637. 2004. View Article : Google Scholar : PubMed/NCBI