4.3 Article

Combined application of cisplatin and salicylic acid suppresses cell growth and promotes apoptosis in human lung cancer cell lines

Journal

BIOLOGIA
Volume 77, Issue 1, Pages 215-223

Publisher

SPRINGER
DOI: 10.1007/s11756-021-00920-9

Keywords

Cisplatin; Lung cancer; P21; Salicylic acid; ZEB1

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Funding

  1. Islamic Azad University, Yadegar-e-Imam Khomeini (RAH) Shahre Rey Branch, Tehran, Iran

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The combined application of cisplatin and salicylic acid showed synergistic effects on lung cancer cell lines A549 and Calu-6, exhibiting efficient inhibition and anti-proliferation effects while promoting apoptosis.
Lung cancer is the leading cause of cancer-related deaths worldwide. Cisplatin-based chemotherapy remains the standard gold method in therapeutic strategy due to the high usefulness of cisplatin, the application, and the dosage of cisplatin regulated by its adverse effects on neurons. In addition, salicylic acid as a nonsteroidal anti-inflammatory drug has also been reported to treat another type of cancer by activating apoptosis mechanisms. In this research, the synergistic function of cisplatin and salicylic acid on apoptosis activity, cytotoxicity of lung cell lines A549 and Calu-6, and molecular expression level of ZEB1 and P21 genes were the main objectives. Lung carcinoma cell lines A549 and Calu-6 were exposed to different concentrations of cisplatin and salicylic acid alone and in combination to evaluate cell viability by MTT assay. Then, the optimal concentration of cisplatin (0.5 mu M) in combination with salicylic acid (2 mM) for apoptotic cells was determined by flow cytometry. Real-time PCR was also performed to conduct the expression analysis of P21 and ZEB1 genes. The combination of the two drugs showed the highest inhibitory and anti-proliferation effects on A549 and Calu-6 cell lines (P < 0.05; P < 0.01, respectively). Gene expression analysis showed that the P21 gene was significantly downregulated in the Calu-6 cell lines and the ZEB1 gene was downregulated only in the A549 cell line (P = 0.01). ZEB1 was overexpressed in the Calu-6. The combined form of cisplatin and salicylic acid significantly suppressed cell proliferation and promoted apoptosis in lung cancer cell lines.

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