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Quercetin and 2-Methoxyestradiol (2-ME) are promising anti-cancer substances. Our previous  in vitro  study showed that quercetin synergized with 2-Methoxyestradiol exhibiting increased antiproliferative and proapoptotic activity in both androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cell lines. In the present study, we determined whether their combination could inhibit LNCaP and PC-3 xenograft tumor growth  in vivo  and explored the underlying mechanism. Human prostate cancer LNCaP and PC-3 cells were inoculated subcutaneously in male BALB/c nude mice. When xenograft tumors reached about 100 mm 3 , mice were randomly allocated to vehicle control, quercetin or 2-Methoxyestradiol singly treated and combination treatment groups. After therapeutic intervention for 4 weeks, combination treatment of quercetin and 2-ME i) significantly inhibited prostate cancer xenograft tumor growth by 46.8% for LNCaP and 51.3% for PC-3 as compared to vehicle control group, more effective than quercetin (28.4% for LNCaP, 24.8% for PC3) or 2-ME (32.1% for LNCaP, 28.9% for PC3) alone; ii) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; iii) led to higher Bax/Bcl-2 ratio, cleaved caspase-3 protein expression and apoptosis rate; and iv) resulted in lower phosphorylated AKT (pAKT) protein level, vascular endothelial growth factor protein and mRNA expression, microvascular density and proliferation rate than single drug treatment. These effects were more remarkable compared to vehicle group. Therefore, combination of quercetin and 2-ME can serve as a novel clinical treatment regimen owning the potential of enhancing antitumor effect on prostate cancer  in vivo  and lessening the dose and side effects of either quercetin or 2-ME alone. These  in vivo  results will lay a further solid basis for subsequent researches on this novel therapeutic regimen in human prostate cancer.

Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth