Ultrasound, computed tomography, magnetic resonance, and gamma scintigraphy-based detection and bio-imaging technologies have achieved outstanding breakthroughs in recent years. However, these technologies still encounter several limitations such as insufficient sensitivity, specificity and security that limit their applications in cancer detection and bio-imaging. The semiconductor quantum dots (QDs) are a kind of newly developed fluorescent nanoparticles that have superior fluorescence intensity, strong resistance to photo-bleaching, size-tunable light emission and could produce multiple fluorescent colors under single-source excitation. Furthermore, QDs have optimal surface to link with multiple targets such as antibodies, peptides, and several other small molecules. Thus, QDs might serve as potential, more sensitive and specific methods of detection than conventional methods applied in cancer molecular targeting and bio-imaging. However, many challenges such as cytotoxicity and nonspecific uptake still exist limiting their wider applications. In the present review, we aim to summarize the current applications and challenges of QDs in cancer research mainly focusing on tumor detection, bio-imaging, and provides opinions on how to address these challenges.

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Aplysin, a bromosesquiterpene isolated from Aplysia kurodai, was explored as a potential anti-breast cancer agent by us. However, the mechanisms underlying the anticarcinogenic effect of aplysin remain unclear. Here, aplysin was found to remarkably suppress tumor growth in vivo , inhibit cell proliferation and promote apoptosis in vitro . Additionally, we demonstrated that aplysin attained these effects in part by down-regulating PI3K/AKT/FOXO3a signaling pathway. Aplysin treatment inhibited the phosphorylation levels of AKT (Ser-473) and AKT-dependent phosphorylation of FOXO3a (Ser-253) in breast cancer cell lines and breast cancer tissues. The expression levels of FOXO3a-targeted genes were also destabilized by aplysin, cyclin D1 and Bcl-XL were declined; however, p21 CIP1 , p27 KIP1 , Bim, TRAIL and FasL were increased both in vivo and in vitro . Furthermore, activation of the PI3K/AKT signaling pathway by an activator and silencing of FOXO3a by shRNA protected the cells from aplysin mediated growth suppression and apoptosis. In summary, our findings revealed that aplysin could suppress breast cancer progression by inhibiting PI3K/AKT/FOXO3a pathway, thereby suggesting a potential role of aplysin as a chemoprevention drug for patients with breast cancer.

Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively. We found that fucoidan treatment decreased the tumor incidence and mean tumor weight and prolonged the tumor latency. Flow cytometric analyses revealed that the number of blood natural killer cells was higher after fucoidan treatment and that the proportions of CD4 and CD8 T cells were also increased. The serum levels of interleukin (IL)-6, IL-12p40, and interferon (IFN)-γ were higher in the rats treated with fucoidan compared to those of model rats. Moreover, the percentage of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and transforming growth factor β in the serum were lower in the rats treated with fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p-phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than those of model rats. These results suggest that a fucoidan-supplemented diet can inhibit DMBA-induced tumors in rats. This study provides experimental evidence toward elucidating the immune enhancement induced by fucoidan through the programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is one of the possible mechanisms of the protective effect of fucoidan against mammary carcinogenesis.

Resistance to endocrine therapy represents a major concern for patients with estrogen receptor α positive (ERα+) breast cancer. Endocrine therapy resistance is commonly mediated by activated E2F signaling. A better understanding of the mechanisms governing E2F1 activity in resistant cells could reveal strategies for overcoming resistance. Here, we identified the long non-coding RNA (lncRNA) actin gamma 1 pseudogene 25 (AGPG) as a regulator of E2F1 activity in endocrine resistant breast cancer. Expression of EGPG was increased in endocrine-resistant breast cancer cells, which was driven by epigenomic activation of an enhancer. AGPG was also abnormally upregulated in patient breast tumors, especially in the luminal B subtype, and high AGPG expression was associated with poor survival of ERα+ breast cancer patients receiving endocrine therapy. The upregulation of AGPG mediated resistance to endocrine therapy and CDK4/6 inhibition in breast cancer cells. Mechanistically, AGPG physically interacted with PURα, thus releasing E2F1 from PURα and leading to E2F1 signaling activation in ERα+ breast cancer cells. In breast cancer patients, E2F1 target genes were positively and negatively correlated with expression of AGPG and PURα, respectively. Co-administration of chemically modified AGPG siRNA and tamoxifen strongly suppressed tumor growth in endocrine resistant cell line-derived xenografts. Together, these results demonstrate that AGPG can drive endocrine therapy resistance and indicate that it is a promising biomarker and potential therapeutic target in breast cancer.