Contract: Banxia Xiexin decoction (BXD), a classic formula clinically applied for gastroenteritis, possesses anti-tumor properties in Colorectal cancer (CRC). However, the exact molecular mechanism remains obscure.
Objective: To explore the effectiveness of BXD in reversing 5-FU resistance in CRC and elucidate its mechanism of action.
Materials and methods: SW620/5-FU resistant cells were cultured. The effects of BXD, 5-FU, and their combination on the proliferation of SW620/5-FU cells were analyzed by the CCK-8 and clone formation assay, including cell apoptosis and cell cycle distribution. The immunofluorescence intensity of High mobility group box 1 (HMGB1) and microtubule-associated protein 1 light chain 3 (LC3) were determined using an immunofluorescence assay, and the expression levels of autophagy-related proteins such as LC3 and beclin-1, P-glycoprotein (P-gp) and apoptosis-related proteins were evaluated using Western blot analysis. The in vivo effect of BXD on tumor growth was investigated using a xenograft mice model.
Results: We demonstrated combining BXD and 5-FU therapy abolished 5-FU resistance in SW620/5-FU cells by triggering cell death, producing G2-phase cell cycle arrest, and lowering P-gp protein expression and activity. Furthermore, in the xenograft mouse model, our results also showed that BXD restrains the HMGB1 signaling pathway, decreases autophagy level, and inhibits the multidrug resistance of CRC.
Conclusion: BXD can increase the sensitivity and reverse the drug resistance of SW620/5-FU, possibly through a mechanism involving cell proliferation, apoptosis, and autophagy, which is the scientific basis for identifying clinical application.
Keywords: Apoptosis; Autophagy; Chemotherapy; Colorectal Cancer; P-glycoprotein (P-gp); Proliferation.
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