Low-temperature plasma-activated medium enhances the chemosensitivity of colorectal cancer cells by improving hypoxia

Studies have demonstrated that the tumour microenvironment is hypoxia and that hypoxia can induce hypoxia inducible factor-1a (HIF-1a) expression and mediate tumour chemoresistance, which leads to a very poor prognosis for cancer patients. In this study, an economical and practical HIF-1a inhibitor, plasma-activated medium (PAM), was prepared, and its role in colorectal cancer (CRC) was investigated in vitro and in vivo. We found that HIF-1a expression significantly increased under hypoxia in CRC cells followed by decreased chemosensitivity to oxaliplatin (OXA). Additionally, PAM could reduce HIF-1a expression induced by hypoxia in CRC cells, and compared to PAM or OXA alone, PAM enhanced the chemosensitivity of OXA both in vitro in CRC cells and in vivo in cell-derived xenografts, as indicated by the inhibition of cell proliferation and tumour growth. Further mechanistic studies re-vealed that PAM might exert synergistic antitumour activity by inhibiting the MAPK pathway, which deserves further elucidation. In summary, PAM displayed prospective clinical application due to its important function in improving hypoxia in CRC.

Automated summary

This study found that the tumor microenvironment is hypoxia, which can induce the expression of hypoxia inducible factor-1a (HIF-1a) and mediate tumor chemoresistance, leading to poor prognosis for cancer patients. A cost-effective and practical HIF-1a inhibitor, plasma-activated medium (PAM), was investigated in colorectal cancer (CRC) in vitro and in vivo. PAM was able to reduce HIF-1a expression induced by hypoxia, enhancing the chemosensitivity of oxaliplatin (OXA) in CRC cells and inhibiting cell proliferation and tumor growth. Mechanistically, PAM might exert synergistic antitumor activity by inhibiting the MAPK pathway.