MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs which play important roles in diverse biological processes and are acting as key regulators of tumorigenesis and chemotherapy resistance. In this study, a downregulation of miR-125b was observed in breast cancer cell lines, suggesting miR-125b is a tumor suppressor in breast cancer. Moreover, the miR-125b levels were significantly decreased in doxorubicin-resistant MCF-7 (MCF-7/DR) cells compared with MCF-7 cells. Transfection of miR-125b significantly enhanced the cytotoxicity of doxorubicin to MCF-7/DR cells. However, the overexpression of miR-125b did not influence the doxorubicin accumulation but downregulated the myeloid cell leukemia-1 (Mcl-1) levels, which may be the mechanism of apoptosis induction caused by doxorubicin combining with miR-125b in MCF-7/DR cells. Furthermore, luciferase reporter assay proved that Mcl-1 is the target of miR-125b. Importantly, we found that the sensitization of miR-125b to doxorubicin cytotoxicity is caspase-dependent in MCF-7/DR cells, which can be inhibited by zVAD-fmk. Finally, we indicated that the treatment of miR-125b plus doxorubicin leads to loss of mitochondrial membrane potential (MMP) and mitochondria outer membrane permeability (MOMP), which were interacted with the activation of caspases. Thus, this study revealed the role of miR-125b in doxorubicin resistance and therapy, which may provide novel approaches for the treatment of breast cancer.

As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.

Background: Postoperative nausea and vomiting (PONV) is a common complication after mastectomy. Although many researches have been studied the prophylactic effect of antiemetics, none of the results are effective. To overcome this problem, dexamethasone was used to relieve the occurrence of PONV. Since concerns about steroid-related morbidity still remain, We carried out a meta-analysis to evaluate the impact of prophylactic dexamethasone on PONV, post-operative pain undergoing mastectomy. Methods: Literature search was conducted through PubMed, Web of Science, EMBASE, MEDLINE, and Cochrane library database till June 2019 to identify eligible studies. Meanwhile, we also consulted some Chinese periodicals, such as China Academic Journals, Wanfang and Weipu. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis guidelines. Randomized controlled trials were included in our meta-analysis. Meanwhile, the assessment of the risk of bias was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version. The pooled data are processed by software RevMan 5.3. Results: Four studies with 490 patients were enrolled to this meta-analysis. Our study demonstrated that the dexamethasone group was significantly more effective than the placebo group in term of PONV (risk ratio [RR] = 0.46, 95% confidence intervals [CI]: 0.30–0.70, P = .0003), nausea (RR = 0.26, 95% CI: 0.10–0.68, P = .006) and vomiting (RR = 0.15, 95% CI: 0.04∼0.55, P = .004). The visual analog scale score was significantly diminished at 1 hour (weighted mean difference = -1.40, 95% CI: -1.53 to -1.26, P < .00001) in the dexamethasone group, while, no statistically significant difference was observed between the two groups in terms of visual analog scale at 24 hours (weighted mean difference = -0.56, 95% CI: -1.24 to 0.13, P = 0.11). Conclusion: Not only does Dexamethasone reduce the incidence of PONV but also decreases postoperative pain. However, we still need larger samples and higher quality studies to determine the relationship between symptoms and administration time to reach the conclusion. Trial registration number: PROSPERO CRD 42018118575

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The main characteristics of cervical cancer are abnormal and uncontrolled cell proliferation, and it regulates cell growth, differentiation, and cell death through genetic and epigenetic changes. This paper mainly discusses the radiosensitivity of the cervical cancer protein kinase B signaling pathway and discusses the specific mechanisms that affect the occurrence and development of cervical cancer. In addition, this paper studies the effect of transient transfection knocking down the expression of TRIP4 in cervical cancer cells on the expression of key proteins in related signaling pathways and explores the mechanism of its specific effects and finds the mechanism of TRIP4’s effect on cervical cancer radiosensitivity. The findings of this study show for the first time that knocking down TRIP4 inhibits cell viability by inhibiting the P13K/AKT and MAPK/ERK pathways, and this corresponds to the first part of the experimental results, which show that knocking down TRIP4 inhibits colony formation and increases apoptosis in HeLa and SiHa cells. Moreover, simultaneous inhibition of TRIP4 and hTERT proteins can increase the radiosensitivity of cervical cancer cells. These findings indicate that the inhibition of TRIP4 may be a new type of treatment that selectively targets the P13K/AKT and MAPK/ERK pathways and hTERT pathways in cervical cancer cells and provides a therapeutic option for the treatment of cervical cancer.