Background: Ovarian cancer is a disease with the highest mortality in gynecologic malignancies.
Activation of STAT3 pathway is well known to be associated with tumor progression
and metastasis in a number of cancers, including ovarian cancer. Therefore, STAT3 may be an ideal
target for ovarian cancer treatment.
Objective: The present study aims to determine the antitumor activity of STAT3 inhibitor Napabucasin
as a single agent or in combination with proteasome inhibitor MG-132 in ovarian cancer
Methods: MTT was performed to determine the anti-proliferative effect of Napabucasin on ovarian
cancer SKOV-3 cells. The involved anti-tumor mechanism was explored by flow cytometry, qRTPCR
and western blot. MDC staining and tandem mRFP-GFP-LC3 fluorescence microscopy were
used to analyze the autophagy-inducing capability of Napabucasin with or without MG-132. The
combinational anticancer effect of Napabucasin and MG-132 was evaluated according to Chou and
Talalay’s method (1984).
Results: Napabucasin showed obvious tumor-inhibitory effects against SKOV-3 cells. Treatment
by Napabucasin arrested cell cycle progression in G2/M phase. Mechanistically, elevated expression
of p21 may contribute to the blockade of the cell cycle. Moreover, we demonstrated that Napabucasin
induced autophagy in SKOV-3 cells by using various assays, including MDC staining,
autophagic flux examination, and detection of the autophagy markers. In addition, a combination
of Napabucaisin with MG-132 exhibited a significant synergistic anti-proliferative effect, probably
by inducing apoptosis through a mitochondria-dependent pathway. The two compounds induced
pro-survival autophagies, and co-treatment with autophagy inhibiter might further enhance their antitumor
Conclusion: Napabucasin alone or in combination with MG-132 might be promising treatment
strategy for ovarian cancer patients.