Fig. 6.

A combination of fluvastatin and aspirin/metformin activates pAMPK and effectively inhibits HMG-COA reductase (HMGCR) in MCF10.DCIS cells. a, b The mevalonate pathway, where statin treatment triggers a restorative feedback loop leading to upregulation of HMGCR mRNA levels (a) and aspirin and metformin put a brake in this restorative feedback loop through activation of AMPK phosphorylation (b) c Western blot showing the endogenous levels of the indicated proteins in the lysates of MCF10.DCIS cells treated with vehicle/fluvastatin (FV) in combination with aspirin or metformin (met) for 48 h. Vinculin was used as the loading control. d Averaged densitometry across multiple western blots for the indicated proteins showing the effect of fluvastatin alone or in combination with aspirin (asp) or metformin (met) on HMGCR and pAMPK levels. HMGCR levels were calculated by normalizing to the loading control vinculin. pAMPK levels were first normalized to vinculin and next a ratio of normalized pAPMK was obtained by dividing with normalized levels of total AMPK. Values represent mean fold change ± SEM. *p < 0.05, **p < 0.01 and ***p < 0.001 as compared to fluvastatin alone