Anthracycline chemicals with anthracyclinone structure exert antitumor effects by inhibiting angiogenesis and lymphangiogenesis in a xenografted gastric tumor model.

Background: It is vital to screen or develop alternative therapeutic drugs with higher curative characteristics and fewer side effects for the clinical treatment of gastric cancer.
Methods: Gastric cancer cells were exposed to different auramycin G doses while determining the impact on cell viability, migration, and invasion. Then the antitumor effects of auramycin G, 5-fluorouracil (5-Fu) and their combination were evaluated. Furthermore, the molecular mechanisms of angiogenesis and lymphangiogenesis regulated by auramycin G and its analogs were investigated.
Results: Auramycin G inhibited cell viability in a dose-dependent manner, with a 50% inhibitory concentration of 23.72 ± 6.36 mg/L and 32.54 ± 5.91 mg/L for AGS and MGC803 cells, respectively. The migration and invasion of gastric cancer cells were significantly inhibited by 10 mg/L auramycin G, which was consistent with the down-regulation of the VEGFR2-VEGFA-pPI3K-pAkt-pErk1 and VEGFR3-VEGFC-pPI3K-pAkt-pmTOR proteins. Notably, the average tumor weights were significantly reduced in both the auramycin G (2.21 ± 0.45 g) of 50 mg/kg body weight and auramycin G + 5-fluorouracil (5-Fu) groups (1.33 ± 0.28 g), compared with the control (3.73 ± 0.56 g). Considering that auramycin G decreased the growth of blood and lymphatic vessels while reducing the degree of tumor malignancy, it effectively suppressed tumors by regulating the angiogenic and lymphangiogenic pathways.
Conclusion: The present study confirmed that auramycin G displayed a prominent antitumor activity in gastric tumor models, both in vitro and in vivo. Moreover, it was confirmed that auramycin G played a specific role in certain gastric cancer cell types, while the mechanism was validated to be associated with angiogenesis- and lymphangiogenesis-related pathway suppression.
(© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)