Study on the Mechanism of Anti-Colorectal Cancer Effects of Anzheng Kangliu Decoction by Inhibiting Glycolysis via PI3K/Akt/mTOR Pathway

OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.

METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu Decoction, and cell proliferation and migration abilities were assessed. Forty-two BALB/c nude mice were randomly divided into a blank control group, model group, 5-fluorouracil (5-FU) group (0.025 g ·kg^-1), Anzheng Kangliu Decoction low-dose group (7.67 g ·kg^-1), medium-dose group (15.34 g ·kg^-1), and high-dose group (30.68 g ·kg^-1). The inhibitory effect of Anzheng Kangliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight, tumor volume, tumor mass, HE staining, immunohistochemical staining of Ki67 and other indicators. High-throughput transcriptome sequencing was performed to identify differentially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group, elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer. Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention. Western blot was employed to detect the expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA) in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.

RESULTS In vitro cell experiments demonstrated that, compared with the blank control group, Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells (P < 0.01), reduced glucose consumption and lactate production (P < 0.05, P < 0.01), and downregulated the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, HK2, and LDHA (P < 0.05, P < 0.01). In vivo animal experiments revealed that, compared with the model group, Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice (P < 0.01), increased tumor tissue necrosis, decreased glucose consumption and lactate production in tumor tissues (P < 0.05, P < 0.01), and reduced the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, HK2, and LDHA (P < 0.05, P < 0.01).

CONCLUSION Anzheng Kangliu Decoction exerts an inhibitory effect on colorectal cancer, and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.