Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway
Authors: Yan Zhang
Weiyuan Ma
Yuhao Dong
Yingshan Liu
Kun Jia
Journal: Experimental and Therapeutic Medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: Akt; PI3K; metformin; proliferation; skin

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&lt;0.05). However, there was no significant change in the mRNA expression of Akt following metformin treatment (P&gt;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&lt;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. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. About 10% of the papers in this journal (n=169 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 3B. Lane 1 in the Akt panel looks remarkably similar to lane 4 in the GAPDH panel. Forensically agrees. ![file] , 
 Corrigendum, [16 May 2022] .  Subsequently to the publication of the above article, an interested reader drew to the authorsu2019 attention that the mRNA bands presented in Fig. 3B appeared to contain an overlapping band held in common, comparing between the Akt and the GAPDH bands. The authors realized that an error had indeed been made during the assembly of the data into this figure; essentially, the incorrect bands had been included in the figure to represent the Akt mRNA expression experiment. In view of the time that has elapsed since this article was published, the authors elected to repeat the agarose gel electrophoresis experiments in question, and have found that the new data supports the same conclusions as those presented in the original paper. The revised version of Fig. 3 is shown opposite, now featuring new data for Fig. 3B, showing the mRNA expression levels of PI3K and Akt in A431 cells following treatment with 45 mM metformin for 12, 24 and 36 h. Note that this error did not have a major impact on either the overall results or on the conclusions reported in this study. The authors regret the errors that were made during the compilation of the data into Fig. 3B. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Experimental and Therapeutic Medicine for granting them the opportunity to publish this; furthermore, they apologize to the readership for any inconvenience caused. ,