Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells

摘要

Lung cancer is the primary malignancy of the lung and is the leading cause of cancer-associated mortality in China. Multidrug resistance (MDR) is an essential aspect of lung cancer treatment failure and a popular topic of investigation in tumor studies. Previous studies have demonstrated that soluble resistance-related calcium-binding protein (Sorcin) is involved in the MDR of various types of human tumor, and that silencing Sorcin was able to reverse the MDR of several types of cultured human cancer cells. However, the effect and potential mechanism underlying the ability of Sorcin to reverse MDR in human lung cancer remains to be fully elucidated. The present study examined the role of Sorcin in the reversal of MDR in human lung cancer A549/DDP cells. The effects included increased drug sensitivity to cisplatin, apoptotic rate, cell cycle arrest in the G2/M phase and intracellular accumulation of rhodamine-123, and decreased expression of multidrug resistance gene 1, lung resistance protein, multidrug resistance-associated protein, glutathione S-transferase pi, ATP-binding cassette transporter A2 (ABCA2), ABCA5, B-cell lymphoma 2 and P-glycoprotein, and the depletion of glutathione in Sorcin-silenced A549/DDP cells. The present study also revealed that there was a downregulation of p-Akt and phosphorylated extracellular signal-regulated kinase (p-ERK), and a decreased transcriptional activation of nuclear factor kappa B, signal transducer and activator of transcription (STAT)3, STAT5 and nuclear factor of activated T-cells following silencing of Sorcin. The results indicated that Sorcin may be used as a potential therapeutic target for MDR through inhibiting the Akt and ERK pathways in human lung cancer.