A Chinese Medicine, Huajie Xiaoliu Formula, Enhances the Anti-Colon Cancer Effect of Tegafur, Gimeracil, and Oteracil Potassium Capsules Through Bcl-2/Bax Signaling Pathway

Research Objective: This study was aimed to determine the main ingredients of Huajie Xiaoliu Formula (HJF) and investigate the anticolon cancer effect of its combination with Tegafur, Gimeracil, and Oteracil Potassium Capsules (S-1) in vivo as well as to preliminarily explore its possiblemechanism. Materials and Methods: The chemical composition ofHJF was determined by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The murine colon carcinoma cell (CT 26.WT) subcutaneous xenograft model of colon cancer mice was established to evaluate the in vivo anti-colon cancer effect of HJF. Evaluation of pathological changes in tumor tissue was evaluated by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expressions of interleukin-1 beta (IL-1 beta), inflammatory cytokines interleukin (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in mice serum. Immunohistochemistry was used to evaluate B cell lymphoma-2 (Bcl-2), Bax, and Ki67 protein expression in tumor tissue. Results: Twenty chemicals in HJF were identified by UPLC-QTOF-MS. In vivo experiments showed that HJF has obvious inhibitory effects on the subcutaneous xenograft model of colon cancer mice. Results of ELISA showed HJF is able to increase mice body weight, inhibit tumor growth, and reduce the serum levels of IL-1 beta and IL-6 along with TNF-alpha. Immunohistochemistry results demonstrated that HJF can significantly inhibit the levels of Bax, Bcl-2, and Ki67 in mice with colon cancer transplant tumors. Furthermore, the combination of HJF and S-1 demonstrated a more significant antitumor effect than any other group in vivo. Conclusions: Huajie Xiaoliu Formula is effective in CT 26.WT subcutaneous xenograft model of colon cancer mice by inhibiting tumorigenesis, metastasis, and angiogenesis through the Bcl-2/Bax signaling pathway, resulting in anti-colorectal tumor effects. Huajie Xiaoliu Formula provides a strong theoretical basis for its clinical use and also provides a basis for further research.