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Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesteroneacetate (MPA) improve cancer cachexia via different mechanisms. We aimed to comparethese two drugs, alone or in combination, in cancer cachexia in mice. Forty maleBABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo,and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinomaand fed for 12 days and then treated with PKRI and MPA alone or in combinationfor 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serumlevels of nutritional markers and cytokines were measured. The tumor growth (volumeand weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than thatof placebo group. Wet weight of gastrocnemius muscle was significantly higherin PKRI and PKRI+MPA-treated than in placebo animals (P&lt;0.01). All tumor-bearingmice had a significantly lower level of blood glucose, higher level of serum triglycerideand lower level of serum albumin compared with healthy control (P&lt;0.001). However,PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucoseand lower level of serum triglyceride compared with placebo group (P&lt;0.001).All tumor bearing mice had a significant higher level of serum TNF-α, IL-1 andIL-6 compared with healthy control (P&lt;0.001). Serum level of TNF-α and IL-6was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P&lt;0.01).PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and mayalleviate cachexia.

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate