Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells.
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 π, 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 κB, 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.
Department of Internal Medicine, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
Yanyan
Y
Gao
Department of Chest Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Wei
W
Li
Department of Chest Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261041, P.R. China.
Xiaobo
X
Liu
Department of Respiratory Medicine, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261041, P.R. China.
Fusheng
F
Gao
Department of Chest Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261041, P.R. China.
Xiaohua
X
Zhao
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D034741:RNA, Small Interfering; C503113:SRI protein, human; D014157:Transcription Factors; D005978:Glutathione; D002945:Cisplatin