Y-D Xu1, J Shang, M Li, Y-Y Zhang. 1. Sterilized Supplying Center, Yantai Yuhuangding Hospital, Yantai, China. zhangyanyun800@sina.com.
Abstract
OBJECTIVE: The development of multidrug resistance (MDR) is a key issue for tumor recurrence and metastasis, leading to treatment failure of gastric cancer (GC). Long non-coding RNA (lncRNA) DANCR has been shown to be highly expressed in GC patients, which accelerates growth and metastasis of GC cells. This study aims to elucidate the role of DANCR in regulating MDR of GC. PATIENTS AND METHODS: The mRNA level of DANCR in GC patients with or without DDP-resistance was determined by quantitative Real-time polymerase chain reaction (qRT-PCR). DANCR expression in GC cell lines (SGC7901, BGC823) and cisplatin (DDP)-resistant cell lines (SGC7901/DDP, BGC823/DDP) was determined as well. Knockdown or overexpression of DANCR in GC cells with or without DDP-resistance was achieved by siRNA interference technology or stable transfection of lentivirus, respectively. The regulatory effects of DANCR on cytotoxicity and apoptosis were examined by cytotoxicity assay and flow cytometry method (FCM), respectively. In addition, we detected the expressions of MDR1, MRP1, mechanistic target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1α) in GC cells overexpressing DANCR by qRT-PCR and Western blot. RESULTS: DANCR expression remained high in DDP-resistant GC tissues or cells. SGC7901/DDP and BGC823/DDP cells transfected with si-DANCR presented decreased survival and increased apoptosis. On the contrary, SGC7901/DDP and BGC823/DDP cells overexpressing DANCR showed increased survival and decreased apoptosis. In addition, DANCR overexpression could upregulate expressions of MDR1 and MRP1 in DDP-induced SGC901 and BGC823 cells. CONCLUSIONS: Upregulation of DANCR can accelerate the MDR development of GC, which may become a potential target for treating GC with MDR.
OBJECTIVE: The development of multidrug resistance (MDR) is a key issue for tumor recurrence and metastasis, leading to treatment failure of gastric cancer (GC). Long non-coding RNA (lncRNA) DANCR has been shown to be highly expressed in GC patients, which accelerates growth and metastasis of GC cells. This study aims to elucidate the role of DANCR in regulating MDR of GC. PATIENTS AND METHODS: The mRNA level of DANCR in GC patients with or without DDP-resistance was determined by quantitative Real-time polymerase chain reaction (qRT-PCR). DANCR expression in GC cell lines (SGC7901, BGC823) and cisplatin (DDP)-resistant cell lines (SGC7901/DDP, BGC823/DDP) was determined as well. Knockdown or overexpression of DANCR in GC cells with or without DDP-resistance was achieved by siRNA interference technology or stable transfection of lentivirus, respectively. The regulatory effects of DANCR on cytotoxicity and apoptosis were examined by cytotoxicity assay and flow cytometry method (FCM), respectively. In addition, we detected the expressions of MDR1, MRP1, mechanistic target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1α) in GC cells overexpressing DANCR by qRT-PCR and Western blot. RESULTS:DANCR expression remained high in DDP-resistant GC tissues or cells. SGC7901/DDP and BGC823/DDP cells transfected with si-DANCR presented decreased survival and increased apoptosis. On the contrary, SGC7901/DDP and BGC823/DDP cells overexpressing DANCR showed increased survival and decreased apoptosis. In addition, DANCR overexpression could upregulate expressions of MDR1 and MRP1 in DDP-induced SGC901 and BGC823 cells. CONCLUSIONS: Upregulation of DANCR can accelerate the MDR development of GC, which may become a potential target for treating GC with MDR.