Osthole Regulates miR-433-3p/Tiam1 to Suppress Colon Cancer Cell Proliferation, Migration and Invasion
WANG Jiazheng1, LIU Xiaoyuan2, ZHANG Lei2*, LIU Panpan2, CHEN Yongxue2, CHEN Heyan2, LI Dongxing2
The aim of this study is to investigate the mechanism of osthole regulating miR-433-3p/Tiam1 (T-cell lymphoma invasion and metastasis-inducing protein 1) to inhibit the proliferation, migration and invasion of colon cancer cells. SW480 cells were cultured in vitro and randomly grouped into control group, low-dose osthole group, high-dose osthole group, miR-433-3p-NC control group, and high-dose osthole+miR-433-3p inhibitor group. After grouping treatment, to detect the proliferation, apoptosis, migration and invasion of SW480 cells in each group, and to detect the expressions of Tiam1 protein, the expressions of apoptosis-related proteins and epithelial-mesenchymal transition-related proteins, the expressions of miR-433-3p and Tiam1 mRNA of SW480 cells in each group. SW480 cells were cultured in vitro and randomly grouped into control group, miR-433-3p mimics group, miR-433-3p mimics+pcDNA group, miR-433-3p mimics+pcDNA-Tiam1 group. After grouping treatment, detect the proliferation, apoptosis, migration and invasion of SW480 cells in each group. The results showed that compared with the control group, the cell survival rate, colony formation rate, migration distance, invasion number, Tiam1 mRNA and protein expressions, PCNA, Claudin-1 and N-cadherin protein expressions in the low- and high-dose osthole groups decreased (P<0.05), the proliferation doubling time, apoptosis rate and apoptosis ratio, the E-cadherin and caspase-3, Bax protein expressions, and the miR-433-3p expression increased (P<0.05), high dose osthole has a stronger effect; miR-433-3p inhibitor can reduce the effects of osthole on the above-mentioned cellular indicators. Upregulation of miR-433-3p can exert the same anti-cancer effect on colon cancer cells as osthol, while overexpression of Tiam1 can weaken the anti-cancer effect of upregulated miR-433-3p on colon cancer cells. The results suggest that osthole down-regulates the expression of Tiam1 by promoting the expression of miR-433-3p, thereby upregulate E-cadherin and caspase-3, Bax protein expression, downregulate PCNA, Claudin-1 and N-cadherin protein expression, ultimately inhibite the proliferation, migration and invasion of colon cancer cells, and promote their massive apoptosis.
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