Mechanism Of PLAC1 Promoting Gastric Cancer Proliferation And Its Therapeutic Potential

OBJECTIVEGastric cancer is the third leading cause of cancer death in the world,and it is especially important to find molecules that related to the development and treatment of gastric cancer.Placenta-specific 1(PLAC1),one of the cancer-testis antigen,which is highly expressed in tumor cells and lowly expressed in normal cells,maybe a potential target for tumor therapy.Therefore,the purpose of this study is to clarify the role and mechanism of PLAC1 in gastric cancer and further explore its therapeutic potential for gastric cancer.METHODSWe firstly explored the expression of PLAC1 in gastric cancer and its clinical prognosis through data mining,moreover,we used western blot to detect the expression of PLAC1 in gastric cancer cell lines SGC-7901 and MGC-803,gastric mucosal epithelial cell line GES-1 and gastric cancer tissues.Then,the expression of PLAC1 was interfered by siRNA,we used colony formation assay,CCK8 cell proliferation assay and flow cytometry to study the changes of cell proliferation in gastric cancer cells,furthermore,PI3K/AKT signaling pathway-related proteins such as p-AKT and cyclinD1 were explored by western blot.Finally,to further investigate whether PLAC1 can be a potential target for the treatment of gastric cancer,we used the PLAC1 antibody for targeted therapy to re-examined cell proliferation and PI3K/AKT signaling pathway-related protein changes.RESULTSData mining showed that PLAC1 was highly expressed in gastric cancer,and patients with high expression of PLAC1 had a worse prognosis.The detection of PLAC1 expression in gastric cancer cell lines and tissues proved that PLAC1 is highly expressed in gastric cancer.After the interference of PLAC1 with siRNA,the number of cell clones was decreased,the CCK8 array results showed that the absorbance(A)value of the test group was 1.114±0.266,the absorbance value of the negative control group was 1.668±0.609,the difference was statistically significant(F=968.9,p <0.001),and flow cytometry showed cell cycle was arrest in G0/G1 phase.Further research show that the expression of PI3K/AKT signaling pathway-associated proteins p-AKT and cyclinD1 were decreased.When targeted therapy with PLAC1 antibody(0?1?2?4ug/ml),the formation of cell clones decreased in a concentration-dependent effect.The results of CCK8 array showed that the absorbance value was 1.104±0.004 in negative control group,0.9578±0.006 in 1ug/ml PLAC1 antibody treatment group,0.876±0.001 in 2ug/ml PLAC1 antibody treatment group and 0.626±0.028 in 4ug/ml PLAC1 antibody treatment group,the cell proliferation ability was weakened in a concentration dependence,the difference was statistically significant(F=576.6,P<0.001).Flow cytometry results also showed that cell cycle was arrest in G0/G1 phase after the targeted therapy of PLAC1 antibody.Then the western blot analysis also showed that the expression of p-AKT and cyclinD1 was decreased.CONCLUSIONPLAC1 is highly expressed in gastric cancer and can promote the proliferation of gastric cancer cells through PI3K/AKT signaling pathway,furthermore it maybe a potential target for gastric cancer treatment.