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

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.

A unified mitochondria mechanistic target of rapamycin acyl‐coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells

“…To determine whether metformin promotes cell apoptosis, HaCaT cells were treated with the indicated concentration of metformin and then analyzed by flow cytometry following annexin V-FITC and PI dual labeling. Similar to previous reports, 17,18 metformin treatment also exerts a dose-dependent increase in the number of apoptotic cells ( Figure 1B and 1C). Moreover, metformin treatment induced cell cycle arrest in the G0-G1 phase in a dose-dependent manner as shown in Figure 1D.…”

Anti‐tumoral effects of exercise on hepatocellular carcinoma growth

“…It has been recognized that it also has antitumor properties. Metformin leads to activation of AMPK, which is a mechanism of action similar to RPA . Accordingly, several studies suggested that metformin enhances the oncologic action of sorafenib.…”

“…Metformin leads to activation of AMPK, which is a mechanism of action similar to RPA. (43)(44)(45) Accordingly, several studies suggested that metformin enhances the oncologic action of sorafenib. Metformin in combination with sorafenib prevented HCC recurrence in mice after surgical resection.…”

Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line

“…A previous report has indicated that metformin may improve treatment resistance in hypoxic cell lines (27). Metformin is widely used worldwide as a therapeutic agent for type 2 diabetes, but also has antitumor effects in some types of cancer cell lines, including cholangiocarcinoma, ovarian cancer, pancreatic cancer, and epidermoid carcinoma (28)(29)(30)(31). Metformin exhibits its antitumor effects via inhibition of mTOR by activation of AMPK (32).…”