Qin Huang formula enhances the effect of Adriamycin in B-cell lymphoma via increasing tumor infiltrating lymphocytes by targeting toll-like receptor signaling pathway

Abstract

Abstract Background As an original traditional Chinese medicinal formula, Qin Huang formula (QHF) is used as adjuvant therapy for treating lymphoma in our hospital and has proven efficacy when combined with chemotherapy. However, the underlying mechanisms of QHF have not been elucidated. Methods A network pharmacological-based analysis method was used to screen the active components and predict the potential mechanisms of QHF in treating B cell lymphoma. Then, a murine model was built to verify the antitumor effect of QHF combined with Adriamycin (ADM) in vivo. Finally, IHC, ELISA, 18F-FDG PET-CT scan, and western blot were processed to reveal the intriguing mechanism of QHF in treating B cell lymphoma. Results The systemic pharmacological study revealed that QHF took effect following a multiple-target and multiple-pathway pattern in the human body. In vivo study showed that combination therapy with QHF and ADM potently inhibited the growth of B cell lymphoma in a syngeneic murine model, and significantly increased the proportion of tumor infiltrating CD4+ and CD8+ T cells in the tumor microenvironment (TME). Furthermore, the level of CXCL10 and IL-6 was significantly increased in the combination group. Finally, the western blot exhibited that the level of TLR2 and p38 MAPK increased in the combination therapy group. Conclusion QHF in combination of ADM enhances the antitumor effect of ADM via modulating tumor immune microenvironment and can be a combination therapeutic strategy for B cell lymphoma patients.

Keywords

• Qin Huang formula
• B-cell lymphoma
• Tumor microenvironment
• Tumor-infiltrating lymphocytes
• Toll-like receptor
• Systemic pharmacology