Antitumor Therapy under Hypoxic Microenvironment by the Combination of 2-Methoxyestradiol and Sodium Dichloroacetate on Human Non-Small-Cell Lung Cancer

الملخص EN

A hypoxic microenvironment is a hallmark in different types of tumors; this phenomenon participates in a metabolic alteration that confers resistance to treatments.

Because of this, it was proposed that a combination of 2-methoxyestradiol (2-ME) and sodium dichloroacetate (DCA) could reduce this alteration, preventing proliferation through the reactivation of aerobic metabolism in lung adenocarcinoma cell line (A549).

A549 cells were cultured in a hypoxic chamber at 1% O2 for 72 hours to determine the effect of this combination on growth, migration, and expression of hypoxia-inducible factors (HIFs) by immunofluorescence.

The effect in the metabolism was evaluated by the determination of glucose/glutamine consumption and the lactate/glutamate production.

The treatment of 2-ME (10 μM) in combination with DCA (40 mM) under hypoxic conditions showed an inhibitory effect on growth and migration.

Notably, this reduction could be attributed to 2-ME, while DCA had a predominant effect on metabolic activity.

Moreover, this combination decreases the signaling of HIF-3α and partially HIF-1α but not HIF-2α.

The results of this study highlight the antitumor activity of the combination of 2-ME 10 μl/DCA 40 mM, even in hypoxic conditions.