PI3K/AKT UP-REGULATES HIF-1Α IN THE INFLAMMATORY MICROENVIRONMENT AND INHIBITS THE PYROPTOSIS OF COLON CANCER CELLS

He Kui^{1, 2, *}, Hao Langsong^{1, 2, *}, Deng Yang², Wang Bo², Li Qiang³, Zhang Heling⁴ 

¹Department of General Surgery, Gui Zhou Provincial People’s Hospital, Guiyang, 550000, China - ²Graduate School of Zunyi Medical University, Zunyi City, 563003, China - ³Department of Hepatological Surgery, Gui Zhou Provincial People’s Hospital, Guiyang, 550000, China - ⁴The fourth hospital of Changsha, Changsha, 410000, China

Objective: To further reveal the mechanism of cancer cell apoptosis we investigated. whether the inflammatory microenvironment in colon cancer tissue can activate the PI3K/Akt signaling pathway, and whether it can regulate cell proliferation via HIF-1α. 

Methods: The pathological structure of colon cancer patients, the recruitment of neutrophils, and the mRNA levels of various inflammatory factors were observed by routine pathological staining, immunofluorescence and real-time quantitative PCR. SW480 cells were treated with TNF-α to simulate the inflammatory microenvironment of colon cancer, and we next interfere with the signal pathway through chemical inhibitors. Western Blot experiments were performed to explore the upstream and downstream relationship between PI3K/Akt and HIF-1α signaling pathways and its influence on cancer cell apoptosis. 

Results: The histopathological structure of colon cancer was disordered and a large number of neutrophils were recruited into colon cancer nests. The PI3K/Akt signaling pathway was activated by the inflammatory microenvironment and further up-regulated HIF-1α, which in turn promoted the proliferation of colon cancer cells; inhibited HIF-1α, and may inhibit the proliferation of cancer cells and promote the scorch of cancer cells. 

Conclusion: We report that that the PI3K/Akt signaling pathway is activated in colon cancer, and up-regulation of HIF-1α can promote the proliferation of colon cancer cells and inhibit the scorch death of cancer cells, while down-regulation of HIF-1α can inhibit the proliferation of colon cancer cells and promote pyroptosis. Therefore, regulating HIF-1α may be a new therapeutic target for colon cancer treatment.