Cholesterol Promotes Colorectal Cancer Growth by Activating the PI3K/AKT Pathway.

Abstract

Globally, the incidence of colorectal cancer (CRC) increases each year, with an unhealthy diet representing one of the major pathogenic risk factors for CRC. Cholesterol is a vital dietary ingredient required to maintain the normal function of the body; however, disturbances in cholesterol levels have been discovered to exert a significant role in tumorigenesis. The present study is aimed at investigating the role of cholesterol in the occurrence of CRC. Briefly, CRC model mice were established through an intraperitoneal injection of azoxyemethane (AOM) and were subsequently either fed a normal diet (ND), high-fat diet (HFD), or high-fat high-cholesterol diet (HFHC). Furthermore, in vitro experiments were performed following the treatment of SW480 and HCT116 cells with cholesterol, and the cell viability and colony formation rate of CRC cells were analyzed. The findings identified that cholesterol levels were increased in CRC tissues compared with adjacent normal tissues. In contrast, the serum levels of cholesterol were decreased in patients with CRC compared with the healthy controls; however, no significant differences were observed in the cholesterol levels between stage I + II and stage III + IV patients with CRC. Notably, CRC model mice fed with an HFD or HFHC recorded a larger body weight compared with those mice fed a ND; however, no significant differences were reported in the number of tumors formed in each group. Furthermore, the tumor size in the HFHC group was discovered to be increased compared with the ND and HFD groups, and HGD and the pathological morphology were the most pronounced in the HFHC group. Moreover, mice in the HFHC group presented the highest ratio of Ki-67-positive staining and the lowest ratio of TUNEL-positive staining compared with those in the two other groups. Cholesterol treatment also increased the cell viability and clonality of SW480 and HCT116 cells. In addition, the protein expression levels of phosphorylated-AKT were upregulated in cholesterol-induced CRC cells and tissues, whereas the treatment with BAY80-6946 attenuated the cholesterol-induced increases in the cell viability, colony formation ability, and tumor size. In conclusion, the findings of the present study suggested that cholesterol may stimulate the progression of CRC by activating the PI3K/AKT signaling pathway; however, cholesterol may not affect the number of tumors formed in CRC. In addition, cholesterol was discovered to mainly affect the advanced stages of CRC rather than the early stages.