MECHANISM OF M2 MACROPHAGES PROMOTING MIGRATION, INVASION AND DRUG RESISTANCE OF GASTRIC CANCER CELLS THROUGH EXOSOMES

Yandong Li¹, Jing Zuo², Chunhong Ren³, Peige Du¹, Liping An¹, Xiao Guo¹, Chunyang Zhang¹, Xiaoguang Dong¹, Xi yan Ding^{1, *}

¹Beihua University, Jilin City 132011, Jilin Province People’s Republic of China - ²Zuojia Town Central Health Center, Jilin City132109, Jilin Province, People’s Republic of China - ³Siping Women and Infant Hospital, Siping City136000, Jilin Province,People’s Republic of China

Objective: To explore the mechanism of M2 macrophages promoting the migration, invasion and drug resistance of gastric cancer cells through exosome transmission. 

Method: The gastric cancer cell line MFC and mouse bone marrow-derived macrophages were cultured to construct the macrophage polarization model in vitro. The cells were divided into three groups; the M2 macrophage group, the M2 macrophage exosomes group, and the control group. The control group and miR-21 overexpression group were obtained after culture. The cell survival rate, apoptosis and the expression of PTEN, PI3K, and Akt were measured. 

Results: Compared with the control + cisplatin group, the cell survival rate of the M2 macrophage + cisplatin group and the M2 macrophage exosome + cisplatin group were significantly increased, and the apoptosis rate was significantly decreased (P < 0.05), and the cell survival rate of the M2 macrophage exosome + cisplatin group was significantly higher than that of the M2 macrophage + cisplatin group, and the apoptosis rate was significantly lower than that of the M2 macrophage + cisplatin group (P < 0.05). Compared with the control group, the cell survival rate, PI3K, and Akt expression levels were significantly increased in the miR-21 overexpression group, while the apoptosis rate and PTEN expression level were significantly decreased (P < 0.05). 

Conclusion: M2 macrophages can transfer apoE through exosomes, activate the PI3K/Akt signaling pathway, and enhance the invasion and migration ability of gastric cancer cells. In addition, miR-21 in exosomes of M2 macrophages can be transferred to gastric cancer cells through exosomes, inhibit PTEN expression, and activate the PI3K/Akt signaling pathway, thus enhancing their resistance to cisplatin.