ABSTRACT
Aim To investigate the effect of silencing circRNA ciRS-7 on cisplatin resistance of gastric cancer cells and its related mechanism. Methods Cisplatin-resistant gastric cancer cells HGC-27/DDP were constructed, ciRS-7 was silenced and HGC-27/DDP cells were treated with cisplatin. Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of ciRS-7 and microrNA-944 (miR-944). Cell counting kit-8 (CCK-8) was used to detect cell survival rate. Clone formation assay was used to detect the number of clones. Western blot was used to detect the protein expression levels of CyclinD1, proliferating cell nuclear antigen (PCNA), B-lymphocytoma-2-associated X protein (Bax), B-lymphocytoma-2 (Bcl-2) and cleaved aspartate-specific cysteine proteinase 3 (cleaved-caspase-3). Flow cytometry was used to detect cell apoptosis rate. In situ end labeling (TUNEL) was used to detect apoptosis index. Dual luciferase assay was used to verify the targeting relationship between ciRS-7 and miR-944. Results CiRS-7 was highly expressed in cisplatin-resistant gastric cancer tissues and cells, while miR-944 was low expressed in cisplatin-resistant gastric cancer tissues and cells. The survival rate, clonal formation number, protein expression levels of CyclinD1, PCNA and Bcl-2 in cisplatin-treated HGC-27/DDP cells were significantly reduced by silencing ciRS-7, while ciRS-7 expression level, apoptosis rate, apoptosis index, Bax, cleaved-caspase-3 protein expression levels of cisplatin-treated HGC-27/DDP cells were significantly raised. CiRS-7 targetedly inhibited the expression of miR-944. Conclusions Silencing ciRS-7 can reverse cisplatin resistance of gastric cancer cells, and the mechanism may be related to the promotion of miR-944 expression by silencing ciRS-7.
ABSTRACT
Objective To investigate the clinical effects of Shenlian capsule,trastuzumab combined with SOX regimen in the treatment for HER-2 positive advanced gastric carcinoma.Methods A total of 314 patients with HER-2 positive advanced gastric carcinoma in our hospital were randomly divided observation group and control group,157 cases in each group.The observation group was treated by SOX regimen and trastuzumab,while the control group was given Shenlian capsule on the base of control group.After treatment,the short-term effects in the 2 groups were evaluated.Before and after the treatment,the levels of SDF-1,CXCR4,FSP-1 and MRP-l4 in the 2 groups were detected.During the treatment,the rates of neurotoxicity,gastrointestinal reaction,liver function injury,renal function injury,rashes and bone marrow suppression were observed in the 2 groups.After the treatment,3 years follow-up was performed,the 1 year survival rate,3 year survival rate,overall survival (OS) and progression-free survival (PFS) were observed.Results After the treatment,the control rate (92.7％ vs.79.9％;Z=3.812,P=0.037) and efficiency rate (78.1％ vs.66.4％;Z=3.712,P=0.039) were significantly higher in treatment group than which in the control group (P＜0.05).After the treatment,the levels of SDF-1,CXCR4,FSP-1,MRP-14 in treatment group were significantly lower than control group (t=4.091,4.310,3.972,3.821,P＜0.05).During the treatment,the rates of neurotoxicity,gastrointestinal reaction,liver function injury,renal function injury,rashes,bone marrow suppression were significantly lower in treatment group than control group (x2=5.182,4.671,4.491,5.091,5.204,4.925,P＜0.05 or P＜0.01).After the treatment,the PFS,OS (t=3.714,3.612,P＜0.05),3 year survival rate (x2=3.105,P=0.043) were significantly higher in treatment group than the control group.Conclusions The Shenlian capsule,trastuzumab combined with SOX regimen has a good effect and low toxic effects in the treatment of HER-2 positive advanced gastric carcinoma,and they could prolong the survival time.