Beneficial action of cinnamic acid against ovarian cancer via network pharmacology analysis and the pharmacological activity assessment.

Naturally occurring cinnamic acid (CA) shows the beneficial potential in the suppression of ovarian cancer (OC). Currently, the in-depth molecular mechanisms of CA to suppress OC are still undescribed entirely. Thus, our research used the preclinical methodology through network pharmacology approach and pharmacological evaluation in vitro to unshroud the anti-OC targets and mechanisms of CA. Our data primarily identified 202 CA targets and 495 OC targets, and additional 45 shared targets in CA and OC were screened as presented in interaction network map. All 11 core targets in CA against OC were identified completely. The enrichment analysis of core targets revealed the biological functions and molecular mechanisms of CA against OC in details, including metabolic recombination and immune microenvironment regulation. Additionally, pharmacological evaluation data in vitro suggested that CA inhibited human OC cell proliferation in the time- and dose-dependent manners. In conclusion, CA can exert antineoplastic effects against OC effectively, and the pharmacological functions may directly actualize through a multi-target and multi-pathway avenue for suppressing OC.

GP96 and SMP30 Protein Priming of Dendritic Cell Vaccination Induces a More Potent CTL Response against Hepatoma.

Heat-shock protein (HSP) GP96 is a well-known adjuvant in immunotherapy. It belongs to the HSP90 family. Our previous study demonstrated that DC pulsed with recombinant senescence marker protein 30 (SMP30) could induce cytotoxic T lymphocytes (CTLs) against liver cancer cells in vitro. In this study, SMP30 and GP96 were subcloned into lentiviruses and transfected into DCs from healthy donors. We included six groups: the GP96-SMP30 group, GP96 group, SMP30 group, DC group, empty vector control group, and hepatoma extracted protein group. We used ELISA to detect cytokines and flow cytometry to assess CD80 and CD86 on DCs and the effect of CTLs. Our vector design was considered successful and further studied. In the SMP30 group, DC expresses more CCR7 and CD86 than the control group; in the SMP30+GP96 group, DC express more CCR7, CD86, and CD80 than the control group. Transfected DCs secreted more TNF-α and interferon-ß and induced more CTLs than control DCs. SMP30 + GP96 effectively stimulated the proliferation of T cells compared with control treatment (P < 0.01). We detected the cytokines TNF-α, TNF-ß, IL-12, and IFN (α, ß, and γ) via ELISA (Figure 5) and verified the killing effect via FCM. Four E : T ratios (0 : 1, 10 : 1, 20 : 1, and 40 : 1) were tested. The higher the ratio was, the better the effects were. We successfully constructed a liver cancer model and tested the CTL effect in each group. The GP96 + SMP30 group showed a better effect than the other groups. GP96 and SMP30 can stimulate DCs together and produce more potent antitumor effects. Our research may provide a new efficient way to improve the therapeutic effect of DC vaccines in liver cancer.

Exploring anti-liver cancer targets and mechanisms of oxyresveratrol: in silico and verified findings.

The aim of current study was to exhume the potential targets and molecular mechanisms of oxyresveratrol, a structurally re-constructed resveratrol, for treating liver cancer through bioinformatics investigation and experimentative validation. To start with, the network pharmacology approach and molecular docking technology were used to uncover all candidate targets of oxyresveratrol to treat liver cancer, accompanied with identified anti-liver cancer targets including estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR). In addition, more pharmacological mechanisms of oxyresveratrol against liver cancer were revealed in details. In experimental verification, the clinical samples of liver cancer showed elevated ESR1, EGFR mRNA expressions. The in-vitro data indicated that intracellular contents of ESR1, EGFR mRNAs in oxyresveratrol-treated liver cancer cells were reduced. Taken together, the bioinformatics and validated findings have highlighted detailed pharmacological targets and molecular mechanisms of oxyresveratrol for treating liver cancer. Following with experimental verification, the identified genes of ESR1, EGFR may function as potential screening anti-liver cancer markers.