Luteolin-Zn Complex Inhibits Invasion and Migration of M2-Like TAMs via the Downregulation of AMPK/mTOR and PI3K/Akt/mTOR Signaling Pathway Under Hypoxia

Purpose: The high mortality rate of malignant tumors is often attributable to the loss of surgical opportunities due to late diagnosis when invasion and metastasis have significantly affected the patient. A hypoxic microenvironment can promote the progression of malignant tumors. This study explored the invasion resistance and migration ability of luteolin-Zn complexes. Methods: We created a low-oxygen environment using a 3-atmosphere incubator. The appropriate drug concentration was determined using the CCK8 experiment. We determined its role in cell invasion and migration through scratch and transwell experiments. Western blotting, polymerase chain reaction, and cellular immunity experiments were used to study the mechanism and its impact on the secretion of invasion and migration factors. Results: Our results indicated that the luteolin-Zn complex significantly reduced MMP2, MMP9, N-Ca, and HIF-1ɑ expression. It also upregulated TIMP1 and E-Ca expression. Moreover, its capabilities may be achieved by regulating the AMPK/mTOR and PI3K/Akt/mTOR signaling pathways. Conclusions: The luteolin-Zn complex was highly resistant to the invasion and migration of M2-like tumor-related macrophages. This may exert a unique influence on mTOR by integrating various signals. This study suggests that the luteolin-Zn complex has a strong anticancer effect under hypoxic conditions.