Effects and mechanism of inhibition of naringin in combination with atorvastatin on prostate cancer cells in vitro and in vivo

Abstract

Background/aimNaringin, a naturally occurring flavanone glycoside, can inhibit oxidative stress and inflammatory reactions. Atorvastatin, which belongs to the class of drugs called statins, is an inhibitor of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase and it has shown anticancer activity in prostate cancer (PCa). The present study investigated whether the combination of atorvastatin and naringin has an effect on inhibiting growth in PCa and the mechanisms underlying this effect. MethodsCell growth was assessed by CCK-8 and trypan blue exclusion assay, and the IC50 of LNCaP and PC-3 cells were determined by MTT assay. Scratch migration and matrigel-coated transwell invasion were used to assess both migration and invasion in prostate cancer cell lines. The expression levels of p-Akt, p-STAT3, survivin, AR, Bcl-2, and Bax in prostate cancer cell lines were determined by Western blot. PC-3 and LNCaP xenografts were applied to assess the effect in vivo. ResultsNaringin in combination with atorvastatin had a synergistic inhibitory effect on growth in the prostate cancer cell lines PC-3 and LNCaP, and the combination more strongly inhibited migration and invasion than either single drug. The combination of atorvastatin with naringin potently inhibited the expression levels of AR, p-Akt, survivin, p-STAT3, and Bcl-2. However, an increase in the level of p-STAT3 was found in the PC-3 cells treated with atorvastatin and naringin alone, which differed from that observed in LNCaP. Moreover, the level of Bax in the prostate cancer cell lines treated with atorvastatin and naringin was higher than in those treated with either drug alone. Atorvastatin or naringin treatment had an inhibitory effect on the growth of PC-3 and LNCaP tumors in vivo, and this was especially true of the combined treatment. ConclusionsThe data suggest that the combination of atorvastatin and naringin may be an effective method for inhibiting the growth of prostate cancer. Further research is needed to determine the mechanism of action of the combination of atorvastatin and naringin.