Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment

Abstract

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-β and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway

“…It is worth noting that the 5-FU (10 mg/kg) group as a positive control did not inhibit tumor growth from MFC sources. Referring to two studies using MFC for tumor formation and both treated with a dose of 5-FU (10 mg/kg), the first study used 5-FU (10 mg/kg, once a day), which significantly decreased tumor size compared to that in the control group 44 , while the second study used 5-FU (10 mg/kg, once every two days), which did not significantly change tumor size compared to that in the control group 45 . A comparison of the two studies revealed that the failure to inhibit tumor growth may be related to the frequency of drug injection, as our study used 5-FU (10 mg/kg, once every two days).…”

Platycodin-D exerts its anti-cancer effect by promoting c-Myc protein ubiquitination and degradation in gastric cancer

“…The cell cycle and apoptosis assays were performed as described previously ( Li et al, 2022 ; Xu et al, 2022 ). Briefly, the PD-treated cells were harvested, washed, and fixed.…”

Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism

“…Mice were monitored for body weight and tumor size (length × width 2 × 0.5) once a week according to the animal protocol. After 4 weeks, the nude mice were sacrificed, and the tissues were collected for detection [ 40 ]. The number of macroscopic nodules was then recorded.…”