Paclitaxel promotes lung cancer cell apoptosis via MEG3-P53 pathway activation
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004 (China)
- Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004 (China)
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004 (China)
Highlights: • Paclitaxel up-regulated the expression of long-chain non-coding RNA maternally expressed gene 3 and P53 in Non-small cell lung cancer cell A549 cell line. • Inhibition of maternally expressed gene 3 attenuated the antitumor activity of PTX. • Overexpression of maternally expressed gene 3 enhanced the anti-tumor activity of paclitaxel. • Maternally expressed gene 3 inhibited the proliferation of A549 cells by activating p53, and inhibition of maternally expressed gene 3 partially attenuated the cytotoxicity of paclitaxel via inhibition of P53. • Maternally expressed gene 3 plays an important role in Reactive oxygen species production and subsequently induces A549 cell death. Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The long-chain non-coding RNA maternally expressed gene 3 (MEG3) is a recognized tumor suppressor. This study aimed to explore the effects of PTX on the expression of MEG3 and its anti-tumor mechanism in lung cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine cell proliferation. Quantitative polymerase chain reaction was used to determine the levels of MEG3 expressions. Western blot and immunofluorescence were used to detect protein levels. Small interfering RNA or pCDNA-MEG3 transfection was used to downregulate or upregulate MEG3 expression. Dichlorof luorescein diacetate was used to detect intracellular reactive oxygen species. Flow cytometry was used to analyze apoptosis. PTX significantly inhibited the proliferation of NSCLC cells and increased the expressions of MEG3 and P53. The downregulation of MEG3 attenuated PTX-induced cytotoxicity, whereas upregulation of MEG3 induced cell death and increased P53 expression. The inhibition of P53 caused no effect on the upstream MEG3 expression. Our results suggest that the MEG3-P53 pathway is involved in the apoptosis of A549 cells induced by PTX.
- OSTI ID:
- 23103529
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 504, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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