Expression of SIRT1 gene in human lung cancer lines enhances their sensitivity to the anticancer effects of cisplatin.

Abstract

Lung cancer is one of the lethal cancers and one of the major causes of cancer-related mortalities across the globe. SIRT1 gene has been reported to be involved in the progression and tumorigenesis of several types of cancers. However, the role of SIRT1 gene is in the progression of lung cancer is poorly understood. Against this backdrop, the present study was designed to investigate the expression of SIRT1 gene in different lung cancer cell lines. Moreover, the relation between the expression of this gene and the sensitivity of lung cancer cell lines to the anticancer effects of cisplatin was also investigated. Expression of SIRT1 gene was determined by quantitative RT-PCR. Protein expression was examined by Western blotting. Anti-proliferative activity was determined by MTT and colony formation assay. Apoptotic populations were determined by annexin V/IP staining and flow cytometry. The results revealed that NCI-H125 showed lowest, NCI-H226 showed moderate, while as NCI-H358 exhibited the highest expression of SIRT1. The three differentially SIRT1 expressing cancer cell lines were subjected to cisplatin treatment. It was observed that cisplatin exhibited the highest anticancer activity against NCI-H125 (IC50, 1.25 µM) and lowest against NCI-H358 (IC50, 4.5 µM). Moreover, cisplatin leads to highest inhibition of colony formation and apoptosis in NCI-H125 and lowest against NCI-H358. Expression of SIRT1 gene determines the sensitivity of lung cancer cells to anticancer effects of cisplatin. This work will pave for understanding the role of SIRT1 gene in cancer progression.