[Antitumor component-Ι in Agkistrodon halys venom inhibits proliferation and migration of cisplatin-resistant gastric cancer cells by downregulating RAI14].

OBJECTIVES

To evaluate the inhibitory effect of antitumor component-Ι in Agkistrodon halys venom (AHVAC-I) on proliferation and migration of cisplatin-resistant gastric cancer cells and explore the underlying mechanism.

METHODS

Cisplatin-resistant MKN-28 (MKN-28/DDP) cells were obtained by continuous exposure of MKN-28 cells to stepwise-increasing concentrations of cisplatin. MKN-28/DDP cells were treated with different concentrations of AHVAC-I, and the changes in proliferation, migration and invasion of the cells were examined with colony-forming assay, CCK-8 assay wound-healing assay, and Transwell assay. Western blotting was performed to examine the effect of AHVAC-I on expressions of epithelial-mesenchymal transition (EMT) markers of MKN-28/DDP cells; the changes in protein and mRNA expression of retinoic acid induced 14 (RAI14) was detected with Western blotting and qRT-PCR.

RESULTS

Treatment with 2, 4, and 8 μg/mL AHVAC-I significantly inhibited proliferative, migratory and invasion abilities and reduced the expressions of EMT markers in MKN-28/DDP cells. Compared with MKN-28 cells, MKN-28/DP cells showed an increased expression of RAI14, which was significantly lowered after treatment with AHVAC-I. Supplementation with exogenous RAI14 obviously attenuated the inhibitory effect of AHVAC-I on proliferation and migration of MKN-28/DDP cells.

CONCLUSIONS

AHVAC-I decreases proliferation and invasion of MKN-28/DDP cells by downregulating RAI14 expression.