Manganese Deficiency Promotes the Progression of Invasive Adenocarcinoma of the Cervix by Enhancing the Inflammatory Response.

OBJECTIVE

We aimed to explore the association between manganese (Mn) and the progression of invasive adenocarcinoma of the cervix (IAC), together with the corresponding mechanisms.

MATERIALS: Venous blood was collected from 65 IAC patients and 65 normal controls (female, participated in physical examination) in the fasting state. The levels of Mn and of inflammatory factors in the venous blood were measured using graphite furnace atomic absorption spectrometry (GAS) and enzyme-linked immunosorbent assay (ELISA), respectively. To investigate the relationships between Mn/inflammatory reactions and tumor progression, IAC patients were divided into two groups (I/II and III/IV) according to tumor grade. In vitro studies were also performed using human cervical cancer (CC) cell lines that were HPV-16 positive (Caski) or negative (C-33A). Following treatment with Mn, cell proliferation was detected by CCK-8, cell apoptosis was examined with flow cytometry, and the level of inflammatory factors was measured using qRT-PCR.

RESULTS

The levels of Mn and of the anti-inflammatory factor interleukin-10 (IL-10) in the blood of IAC patients were lower than in normal controls, whereas levels of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were higher. Additionally, the serum electrolyte concentrations of Ca, Mg and K were lower in most IAC patients. The blood Mn level was positively correlated with IL-10, but negatively correlated with IL-6 and TNF-α. Higher Mn level and mild inflammatory response were associated with lower tumor grade. Human CC cells treated in vitro with Mn showed reduced cell proliferation ability, increased apoptosis abilities, and reduced inflammatory reaction.

CONCLUSION

Mn deficiency may enhance the inflammatory reaction that could in turn promote the progression of IAC.