Abstract
Purpose : To investigate the effect of cisplatin on cell toxicity and metastasis through modulation of KAI1 gene expression. Methods: MCF-7cells were incubated with different concentrations of cisplatin for 24 h. RNA was extracted by trizol and cDNA synthesized. KAI1 and TBP were chosen as target and internal control genes, respectively. Specific primers were designed by primer express software, v.3.0. KAI1/TBP and gene expression ratio was calculated using the formula, 2 -∆∆Ct . Results: Cisplatin exerted a dose-dependent inhibitory effect on the viability of highly metastatic MCF-7 cells. KAI1/TBP gene expression ratios were 1.97 ± 0.19 (p < 0.05), 2.96 ± 0.55 (p < 0.05), 9.06 ± 0.27 (p < 0.001) and 12.38 ± 0.88 (p < 0.01) in 10, 20, 50 and 100 µM concentrations of cisplatin. Conclusion: These findings indicate that cisplatin can inhibit metastasis by up-regulating KAI1 gene in MCF-7cells.
Highlights
Cancer is one of the highest causes of mortality in the world
Cisplatin cytotoxicity on MCF-7cells Various concentrations of cisplatin (0, 10, 20, 50 and 100μM) at 24 h were cytotoxic to breast cancer cells (MCF-7cell line)
At concentrations of 10, 20, 40, 80 and 100 μM of cisplatin MCF-7cell viability was reduced to 84.0 ± 12.4, 67.2 ± 12.4 (p < 0.05), 35.6 ± 3.4 (p
Summary
Cancer is one of the highest causes of mortality in the world. The high morbidity and mortality associated with breast cancer derive from its metastasis to lungs, bone and liver [2]. Metastasis is the major cause of death in human cancer patients and involves several stages, including loss of intracellular adhesion in the primary tumor region, migration into lymphatic or blood vessels, adhesion to the surface of the luminal endothelium, and invasion of other organ tissues [3]. Cisplatin (cis-diamminedichloroplatinum or cis-DDP/CDDP) is an anti-cancer drug widely used in the treatment of various cancers, including breast, testicular, ovarian, cervical, prostate, head and neck, bladder, and lung cancers [4]. Cisplatin can cause DNA damage by forming drug-DNA adducts and lead to apoptosis and/or necrosis. Cisplatin-induced cell death has been linked with ceramide-, mitochondria- and death receptor-mediated apoptosis, depending on the cell type being tested [5]
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