Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Objective To explore the correlation of liver depression grading with estrogen receptor alpha and beta(ERα,ERβ)and G protein-couple receptor 30(GPR30)of the perimenopausal women suffering from non-organic insomnia. Methods A total of 127 perimenopausal women suffering from non-organic insomnia were enrolled into the study. The data collected by four diagnostic methods and the scores of Pittsburgh Sleep Quality Index(PSQI)were used for the scoring and grading of liver depression according to Syndrome Element Differentiation. The mRNA and protein expression levels of ERα,ERβand GPR30 in the mononuclear cells of peripheral blood from the patients were detected with real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB)method respectively. Results (1)The differences of mRNA levels of ERα,ERβ and GPR30 were insignificant among the patients with different degrees of liver depression (P > 0.05). ERα mRNA/ERβ mRNA ratio was decreased with the increase of liver depression grading,the differences being significant (F = 6.710, P < 0.001). (2) The differences of protein levels of ERα, ERβ and GPR30 were insignificant among the patients with different degrees of liver depression (P > 0.05);ERα/ERβ protein gray value ratio was decreased with the increase of liver depression grading, and the differences were significant (P < 0.05) . Conclusion The decline of ERα/ERβ is probably contributed to the pathological basis of liver depression in perimenopausal non-organic insomnia women.