Patients diagnosed with ovarian clear cell
carcinoma (OCCC), a rare histologic subtype of
ovarian cancer, often experience poor prognosis owing to the chemoresistance of their disease. Thus, there is an urgent need to identify new therapeutic options for these patients. A
drug screen of 172 traditional Chinese herbs identified
resibufogenin as a compound that inhibited the growth of cultured OCCC cells.
Resibufogenin, a bioactive compound originally isolated from
toad venom, is used in
traditional Chinese medicine to treat several
malignancies. The current study examined the impact of
resibufogenin treatment on proliferation, migration, and invasion of ES-2 and TOV-21G OCCC cells in vitro. Flow cytometric analyses were employed to determine if
resibufogenin affects apoptosis in OCCC cells. Additionally, the ability of
resibufogenin to inhibit
tumor growth in vivo was evaluated in murine xenograft models.
RNA sequencing, quantitative polymerase chain reactions (qPCR), immunohistochemical assays, and western blotting were used to identify and verify cellular pathways potentially targeted by
resibufogenin.
Resibufogenin inhibited proliferation, migration, and invasion of OCCC cells, and induced apoptosis in them.
Resibufogenin also suppressed the growth of xenograft
tumors, which consequently showed lower Ki-67 and higher
terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) expression. We observed down-regulation of (a) PI3K and AKT in the PI3K/AKT signaling pathway, and (b) MDM2 and
myosin in the actin cytoskeleton pathway upon
resibufogenin treatment. Thus,
resibufogenin inhibits growth and migration of OCCC cells in vitro and suppresses OCCC growth in vivo through the PI3K/AKT and actin cytoskeleton signaling pathways.