Downregulation of Inhibition of Apoptosis-Stimulating Protein of p53 (iASPP) Suppresses Cisplatin-Resistant Gastric Carcinoma In Vitro
Jianyong Yu, Li Li, Chengsuo Huang
Department of General Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Qingdao, Shandong, China (mainland)
Med Sci Monit 2017; 23:5542-5549
Gastric cancer (GC) with cisplatin resistance is one of the leading causes of limitations to therapy. Inhibition of apoptosis-stimulating protein of p53 (iASPP) plays a key role in GC. However, the role of iASPP in GC with cisplatin resistance remains unclear. The aim of this study was to investigate iASPP expression in GC, and the functions of iASPP in cisplatin-resistant cell lines.
MATERIAL AND METHODS: In this study, the expression of iASPP was investigated in normal GC patients and patients with cisplatin resistance, along with GC cell lines and cell lines with cisplatin resistance. Furthermore, knockdown of iASPP was conducted in cell lines; and cell proliferation, apoptosis rate, cell cycle distribution, and cell migration and invasion were determined through CCK8, flow cytometry, Scratch test and Transwell assay, respectively.
RESULTS: The expression of iASPP in GC patients with cisplatin resistance was significant higher than in the health control group. Higher expression of iASPP was detected in cisplatin-resistant cancer cell lines. Cell proliferation of SGC-7901 and MGC-803 was inhibited by transfection with siRNA, along with evaluated apoptosis rate and G1 phase retardant. Furthermore, cells viability, including migration and invasion, was suppressed post-transfection with siRNA.
CONCLUSIONS: iASPP induced cisplatin resistance in GC patients. Thus, knockdown of iASPP might be a novel therapeutic strategy for the treatment of GC cisplatin-resistant patients.
Keywords: Cell Cycle, Cell Proliferation, Cisplatin, Drug Resistance, Stomach Neoplasms