Downregulation of MACC1 expression enhances cisplatin sensitivity in SKOV-3/DDP cells

Abstract

ABSTRACT. The aim of this study was to investigate the correlation between MACC1 expression and resistance to cisplatin (DDP) in DDPresistant human epithelial ovarian cancer SKOV-3 cells (SKOV-3/DDP). MACC1 mRNA and protein expression levels in SKOV-3 and SKOV-3/DDP cells were detected by reverse transcriptase polymerase chain reaction and western blot. The SKOV-3/DDP cells were divided into 5 groups: control, shVect (transfected with p-super-EGFP-1 plasmid), pshMACC1 (transfected with psuper-EGFP-shMACC1 plasmid), PD (pretreated with 20 μM PD98059), and combined (transfected with psuper-EGFPshMACC1 plasmid and pretreated with 20 μM PD98059) groups. Cisplatin sensitivity and cell apoptosis in SKOV-3/DDP cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. ERK1/2 and p-ERK1/2 expression was determined by western blot. MACC1 mRNA and protein expression levels in SKOV-3/ DDP cells were 2.66 ± 0.54 and 1.95 ± 0.45 times those seen in SKOV-3 cells (P < 0.05). Cisplatin sensitivity of pshMACC1 group was much higher than that in the control and shVect groups. Cisplatin-induced cell apoptosis rates increased significantly in the pshMACC1, PD, and combined groups, compared to the control and shVect groups. Moreover, the apoptosis rate 17134-17144 (2015) was the highest in the combined group among the 5 groups (IC 50 = 20.836 ± 0.629 μM). p-ERK1/2 expression decreased significantly in the pshMACC1, PD, and combined groups (this decrease was the most obvious in the combined group). In conclusion, downregulation of MACC1 expression could enhance cisplatin sensitivity and decrease drug resistance in SKOV-3/DDP cells.

MACC1 decreases the chemosensitivity of gastric cancer cells to oxaliplatin by regulating FASN expression

“…In fact, this is not the first time MACC1 has been found to play a role in drug resistance. It was reported that MACC1 overexpression induced cisplatinum resistance in ovarian cancer (28,29). Therefore, it is possible and reasonable that MACC1 contributes to oxaliplatin resistance in GC.…”

LncRNA SRA mediates cell migration, invasion, and progression of ovarian cancer via NOTCH signaling and epithelial–mesenchymal transition

“…Ovarian cancer is associated with malignant tumor mortality in women worldwide. According to the GLOBOCAN series reported by the International Cancer Institute, female cancer has a relatively poor prognosis with a 32.5% mortality rate [ 1 ]. Ovarian cancer is one of the most typical gynecological malignancies, with 21750 newly diagnosed cases each year, leading to high morbidity and mortality.…”