Thymoquinone Enhances the Antitumor Activity of Apatinib Against Gastrointestinal Tumors Through the STAT3 Pathway

Objective: To explore the synergistic antitumor activity and mechanism of thymoquinone in combination with apatinib. Methods: Cell proliferation, migration and invasion, apoptosis, and cycle of thymoquinone were investigated by using the CCK8 assay, flow cytometry, scratch assay, Transwell, qRT-PCR and Western blot. The anti-tumor activity of thymoquinone combined with apatinib was investigated by animal tests and immunohistochemistry based on subcutaneous xenografts models of gastric (GC) and colorectal (CRC) cancer cells. Results: Apatinib inhibited proliferation, migration, and invasion of HGC-27 (GC) and HCT116 (CRC) cells, blocked cycle progression, and suppressed the growth of transplanted tumors. Thymoquinone combined with apatinib inhibited proliferation, migration and invasion of HGC-27 and HCT116 cells, arrested cell cycle, and blocked the growth of transplanted tumors. Also, thymoquinone enhanced the antitumor activity of apatinib against gastrointestinal tumors via the JAK2/STAT3 signaling pathway. Conclusion: Thymoquinone enhanced the antitumor activity of apatinib against gastrointestinal tumors, thereby inhibiting the growth of gastrointestinal tumors.