背景:筛选或开发具有更高疗效和更少副作用的替代治疗药物对于胃癌的临床治疗至关重要。
方法:将胃癌细胞暴露于不同剂量的金霉素G,同时确定对细胞活力的影响,迁移,和入侵。然后研究了金霉素G的抗肿瘤作用,评价5-氟尿嘧啶(5-Fu)及其组合。此外,研究了金霉素G及其类似物调节血管生成和淋巴管生成的分子机制。
结果:奥霉素G以剂量依赖性方式抑制细胞活力,对AGS和MGC803细胞的50%抑制浓度分别为23.72±6.36mg/L和32.54±5.91mg/L,分别。10mg/L的金霉素G能显著抑制胃癌细胞的迁移和侵袭,这与VEGFR2-VEGFA-pPI3K-pAkt-pErk1和VEGFR3-VEGFC-pPI3K-pAkt-pmTOR蛋白的下调一致。值得注意的是,在50mg/kg体重的金霉素G(2.21±0.45g)和金霉素G5-氟尿嘧啶(5-Fu)组(1.33±0.28g)中,平均肿瘤重量均显着降低,与对照组相比(3.73±0.56g)。考虑到金霉素G降低了血液和淋巴管的生长,同时降低了肿瘤的恶性程度,它通过调节血管生成和淋巴管生成途径有效抑制肿瘤。
结论:本研究证实,金霉素G在胃肿瘤模型中表现出突出的抗肿瘤活性,在体外和体内。此外,已经证实,金霉素G在某些胃癌细胞类型中起着特定的作用,而该机制被证实与血管生成和淋巴管生成相关途径抑制有关.
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.
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.
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.
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.