Abstract
The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.
Highlights
The incidence of gastric cancer is extremely high in China, posing a severe public health problem
The present study showed that both aspartate transaminase (AST) and ALT, which are indicators of hepatotoxicity [20], declined after the combined administration of Sodium selenite (SS) and PADM (Figure 2), suggesting that combined treatment may reduce the toxicity of SS and PADM
The present study suggested that individual administration of SS or PADM reduced the level of lactate dehydrogenase (LDH) (Figure 2), but the effects were accentuated by combined treatment, effectively inhibiting gastric cancer cell proliferation and promoting cell apoptosis
Summary
The incidence of gastric cancer is extremely high in China, posing a severe public health problem. The strong heterogeneity of gastric cancer [1, 2] has resulted in a low rate of successful treatment via strategies such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Many well-established chemotherapeutic agents have been applied to combat cancer, including doxorubicin (or Adriamycin, ADM), an anthracycline antibiotic. ADM is one of the most important first-line chemotherapeutic drugs with an effective rate of 40–50% in cancer treatment. The newly developed doxorubicin/Adriamycin prodrug, Ac-Phe-Lys-PABC-ADM (PADM), is an effective and low-toxicity chemotherapeutic drug that exhibited high ADM targeting. PADM has been shown to be effective in the treatment of gastric cancer with low toxicity [5] and exhibits potential as a chemotherapeutic agent
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