ABSTRACT
With the deepening research of comprehensive treatment for gastric cancer, the FLOT regimen has begun to be used for the treatment of gastric cancer patients. FLOT neoadjuvant regimen can significantly improve the R 0 resection rate and prolong the overall survival time of locally advanced gastric cancer patients. FLOT regimen combined with immune-checkpoint inhibi-tors, targeted therapy and hyperthermic intraperitoneal chemotherapy have great potential in neo-adjuvant therapy for gastric cancer. The authors systematically analyse the development history and latest clinical research progress of FLOT neoadjuvant regimen for gastric cancer based on their clinical practice experience.
ABSTRACT
OBJECTIVE: To investigate inhibitory effect of FLOT1 gene expression on invasion and apoptosis of gastric cancer cells. METHODS: The designed FLOT1 siRNA lentiviral vector (si-FLOT1 group) was transfected into human gastric cancer MKN-45 cells, at the same time, the negative control lentivirus vector (negative group) was transfected, and the blank group was set up. Western blotting was used to detect the expression of FLOT1, E-cadherin, α-SMA, cleaved caspase 3, Bcl-2 and Bax proteins. After cells were transfected for 24, 48, 72 and 96 h, cell viability was detected by CCK-8 assay. After cells were transfected for 48 h, transwell chamber, flow cytometry and DCFH-DA assay were used to detect the invasiveness, apoptosis rate and ROS content, respectively. RESULTS: FLOT1 siRNA lentiviral vector inhibited significantly the expression of FLOT1 in MKN-45 cells, which was significantly different from the blank group (P<0.05). Compared with si-FLOT1 group and the blank group, the cell vitality decreased, the invasion ability decreased, the apoptosis rate increased, the expression of E-cadherin, cleaved caspase 3 and Bax protein increased, the expression of α-SMA and Bcl-2 protein decreased, and the content of ROS increased, and the difference was statistically significant (P<0.05). CONCLUSION: Down regulation of FLOT1 gene expression can reduce the invasiveness of gastric cancer cells by inhibiting EMT, and promote apoptosis by regulating the expression of apoptosis related proteins and increasing the ROS content of cells.
ABSTRACT
@# Objective: To investigate the expression of Flotillin-2 (Flot-2) protein in gastric cancer tissues and its relationship with clinicopathological features and prognosis of gastric cancer (GC) patients. Methods: 112 samples of gastric cancer tissue and the corresponding paracancerous tissue that resected at the gastrointestinal surgery department of the Second Affiliated Hospital of Nanchang University between January 2009 andApril 2010 were collected for this study. The expression of Flot-2 protein in tumor tissues was detected by immunohistochemistry. The survival data were analyzed by Kaplan-Meier and Log-Rank test, and the survival curve was plotted. Spearman correlation analysis was used to examine the relationship between Flot-2 protein expression and clinicopathological characteristics and prognosis of GC patients. Results: In gastric cancer tissues, Flot-2 was primary stained in cytoplasm. Level of Flot-2 was significantly higher in gastric cancer tissues compared with that in paracancerous tissues (53.57% vs 46.43%, P<0.05). Expression of Flot-2 in tumor tissues was significantly associated with tumor size, depth of invasion, lymph node metastasis, distant metastasis and AJCC stage (all P<0.01), but not with gender, age, differentiation degree and tumor location (P>0.05). Moreover, survival analysis showed that the overall survival of patients with low Flot-2 expression was significantly higher than that of the patients with high level (P<0.01). Cox regression analysis indicated that distant metastasis, AJCC stage and Flot-2 expression were the independent risk factors for the prognosis of GC patients. Conclusion: Flot-2 protein was highly expressed in gastric cancer tissues and closely correlated with the poor prognosis of GC patients; Flot-2 is an independent risk factor for GC prognosis and may be served as a potential therapeutic target for gastric cancer.