EXPRESSION OF CELL ADHESION MOLECULE 4 IN GASTRIC CANCER TISSUE AND ITS EFFECT ON APOPTOSIS, AUTOPHAGIA, INVASION AND METASTASIS OF GASTRIC CANCER CELL LINE BGC-823

Jie Song¹, Wei-guo Dong^{1, *}, Rui-Fang Guo², Hong Nie³

¹Department of Gastroenterology, Renmin Hospital of Wuhan University, WuHan, China - ²Department of Nutrition, Inner Mongolia People's Hospital, Inner Mongolia, China - ³Department of Gastroenterology, Inner Mongolia People's Hospital, Inner Mongolia, China

Objective: To observe the effect of cell adhesion molecule 4 (CADM4) on apoptosis, autophagy, invasion and metastasis of gastric cancer BGC-823 cells. 

Methods: Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of CADM4 in 60 cases of gastric cancer and paracancerous tissues, and the expression of CADM4 in 7 gastric cancer cell lines (HGC-27, BGC-823, MKN45, MGC-803, SGC-7901, NCL.N87, AGS) and normal gastric mucous membrane cells were detected. The overexpression of lentivirus carrier (LV-CADM4) by CADM4 was transiently transferred into BGC-823cells, and the expression of CADM4 mRNA was detected by Real-time PCR. Apoptosis rate and mitochondrial membrane potential were detected by flow cytometry, apoptosis, autophagy and expression of invasion and metastasis related proteins were detected by Transwell invasion test and cell scratch test.; Western blot was used to detect apoptosis, autophagy and expression of invasion and metastasis related proteins. 

Results: The expression level of CADM4 mRNA in gastric cancer was 0.32±0.05, which was significantly lower than that in paracancerous tissues (1.24±0.011) (P<0.001). The expression level of CADM4 in gastric cancer cells was significantly lower than that in HGC-27, MKN45, MGC-803, SGC-7901, NCL.N87, AGS and GES.1 cells (P<0.001). Compared with the blank control group and negative virus group, LV-CADM4 could significantly increase the apoptosis rate of BGC-223 cells (all P<0.001), at the same time, the mitochondrial membrane potential and the ability of invasion and metastasis of BGC-823 cells were significantly decreased (P<0.001). The expression of B cell lymphoma/leukemia-2 (bcl-2), p62, matrix metalloprotease (MMP)-9 protein, bcl-2-associated X protein (bax), cysteinyl aspartate specific protease (Caspase)-9 and microtubule related protein 1 light chain 3 were significantly down-regulated (all P<0.001). 

Conclusion: The expression of CADM4 is down-regulated in gastric cancer tissues and cell lines. Up-regulation of CADM4 can induce apoptosis and autophagy of gastric cancer BGC-823 cells through mitochondrial pathway, and decrease the ability of invasion and metastasis of gastric cancer cells.