Objective: To investigate the effect and mechanism of betulinic acid (BA) on epithelial-mesenchymal
transition (EMT) in A2780 ovarian cancer cells. Methods: The viability of A2780 cells treated with different
concentrations of betulinic acid (5–80 μmol/L) for 24 hours was assessed by using the CCK-8 assay. The effects of
BA on epithelial-mesenchymal transformation were detected under treatment with 0, 5, 10, 20 μmol/L of BA for 24 h.
The transforming growth factor-β (TGF-β) subtype involved in ovarian cancer was predicted by Oncomine, and the
mRNA levels of TGF-β2 in A2780 cells treated with BA (0, 5, 10, 20 μmol/L) for 24 hours were measured. A2780
cells were divided into control group, 10 μmol/L BA group, and 10 μmol/L BA+2 ng/mL TGF-β2 group to determine
whether TGF-β2 could reverse the effect of BA on epithelial mesenchymal transformation, invasion, migration and drug
resistance in A2780 cells. Results: BA decreased the cell viability of A2780 with an IC50 of 37.8 μmol/L. Compared
with 0 μmol/L BA group, the expression of E-cadherin was increased, while N-cadherin, Vimentin were significantly
decreased in the 10 μmol/L and 20 μmol/L BA groups. Oncomine prediction results showed significant differences in
both DNA copy numbers and mRNA expression levels of TGF-β2 between ovarian cancer and normal tissue. Compared
with 0 μmol/L BA group, the expression of TGF-β2 were significantly decreased in the 5, 10, 20 μmol/L BA groups.
Compared with the 10 μmol/L BA group, the 10 μmol/L BA +2 ng/mL TGF- β2 group had decreased E-cadherin,
increased protein expression of N-cadherin, Vimentin, MMP-2, MMP-9, Smad2, Smad3, along with increased numbe r of
invaded cells, enhanced wound healing rate, and improved viability of cisplatin-treated cells. Conclusion: BA may exert
its anti-tumor effects by inhibiting the TGF-β2-associated EMT signaling, thereby reducing the invasion, migration, and
drug resistance of A2780 ovarian cancer cells.
