Open Access

Overexpression of PTEN may increase the effect of pemetrexed on A549 cells via inhibition of the PI3K/AKT/mTOR pathway and carbohydrate metabolism

  • Authors:
    • Bo Li
    • Junkai Zhang
    • Ya Su
    • Yiling Hou
    • Zhenguo Wang
    • Lin Zhao
    • Shengkai Sun
    • Hao Fu
  • View Affiliations

  • Published online on: August 26, 2019     https://doi.org/10.3892/mmr.2019.10617
  • Pages: 3793-3801
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is one of the leading causes of tumor‑associated mortality, and >75% of patients with lung cancer have non‑small cell lung cancer (NSCLC). Pemetrexed, a folate antagonist, is a first‑line chemotherapy drug for NSCLC that is administered alone or in combination with cisplatin. The present study established in vitro cell models of PTEN inhibition and overexpression, and the effects of the treatment with pemetrexed were investigated in these cell models. Result from the present study demonstrated that treatment with pemetrexed suppressed lung cancer cell proliferation, inhibited mRNA and protein expression levels of anti‑apoptotic Bcl2, and increased the mRNA and the protein expression levels of pro‑apoptotic p53 and apoptosis regulator BAX. The present study suggested that pemetrexed regulated apoptosis via the inhibition of the mTOR/PI3K/AKT signaling pathway. Additionally, cellular processes associated with the aerobic oxidation of carbohydrates were identified to be significantly inhibited. The present findings suggested that treatment with pemetrexed may exhibit synergistic effects with PTEN on lung cancer cells via the inhibition of the PI3K/AKT/mTOR signaling pathway and through carbohydrate metabolism, and treatment with pemetrexed combined with PTEN overexpression may represent a novel therapeutic strategy for the treatment of NSCLC.

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October 2019
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Copy and paste a formatted citation
APA
Li, B., Zhang, J., Su, Y., Hou, Y., Wang, Z., Zhao, L. ... Fu, H. (2019). Overexpression of PTEN may increase the effect of pemetrexed on A549 cells via inhibition of the PI3K/AKT/mTOR pathway and carbohydrate metabolism. Molecular Medicine Reports, 20, 3793-3801. https://doi.org/10.3892/mmr.2019.10617
MLA
Li, B., Zhang, J., Su, Y., Hou, Y., Wang, Z., Zhao, L., Sun, S., Fu, H."Overexpression of PTEN may increase the effect of pemetrexed on A549 cells via inhibition of the PI3K/AKT/mTOR pathway and carbohydrate metabolism". Molecular Medicine Reports 20.4 (2019): 3793-3801.
Chicago
Li, B., Zhang, J., Su, Y., Hou, Y., Wang, Z., Zhao, L., Sun, S., Fu, H."Overexpression of PTEN may increase the effect of pemetrexed on A549 cells via inhibition of the PI3K/AKT/mTOR pathway and carbohydrate metabolism". Molecular Medicine Reports 20, no. 4 (2019): 3793-3801. https://doi.org/10.3892/mmr.2019.10617