Triacanthine enhances the sensitivity of colorectal cancer cells to 5-fluorouracil by regulating RRM2.

BACKGROUND: According to the literatures, triacanthine is isolated from the leaves of Gleditsia triacanthos L. and acts as an anti-hypertensive agent, also cardiotonic, antispasmodic and a respiratory analeptic. The 5-fluorouracil (5-FU) is widely used to treat the patients of colorectal cancer (CRC), but the resistance to 5-FU treatment restricts the therapeutic efficacy of CRC patients. PURPOSE: This study aims to explore a novel therapeutics regimen overcoming CRC resistance to 5-FU. METHODS: The cell proliferation of CRC cells was determined by SRB and colony formation assay. Transwell and wound-healing assay were applied to explore the potential metastatic abilities of CRC cells. qRT-PCR and Western blot were performed to evaluate the level of indicated mRNAs and proteins respectively. Xenograft assay was used to explore the anti-CRC effect of triacanthine. RESULTS: Triacanthine statistically restrained CRC proliferation both in vitro and in vivo. Triacanthine induced cell cycle G1/G0 phase arrest in CRC cells. Meanwhile, triacanthine also inhibited the migrative and invasive abilities of CRC cells. A Venn diagram was generated showing that O-6-Methylguanine-DNA Methyltransferase (MGMT) might be a molecular target of triacanthine in treating CRC. Furthermore, triacanthine plus 5-FU significantly suppressed the cell proliferation of CRC cells compared with single agent treatment alone, and highly synergistic anti-cancer effects were scored when 5-FU was combined with triacanthine in CRC cells. In addition, triacanthine sensitized the anti-cancer activity of 5-FU via regulating Ribonucleotide Reductase Regulatory Subunit M2 (RRM2). MGMT or RRM2 might be novel biomarkers for evaluating the therapeutical efficiency of 5-FU in CRC patients. CONCLUSION: We firstly demonstrated triacanthine suppressed cell proliferation and metastasis abilities and found the novel molecular targets of triacanthine in CRC cells. This is the first study to evaluate the anti-cancer efficiency of triacanthine plus 5-FU. Our study has revealed triacanthine as a pertinent sensitizer to 5-FU, and provided novel strategies for predicting outcomes and reversing resistance of 5-FU therapy.

Effectiveness of mindfulness-based interventions on anxiety, depression, and fatigue in people with lung cancer: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the most common cancers and poses a physical and psychological threat to patients. Mindfulness-based interventions are emerging forms of psychotherapy that are effective in improving physical and psychological symptoms, but no review has summarized their effectiveness on anxiety, depression, and fatigue in people with lung cancer. OBJECTIVES: To evaluate the effectiveness of mindfulness-based interventions in reducing anxiety, depression, and fatigue in people with lung cancer. DESIGN: Systematic review and meta-analysis. METHODS: We searched the PubMed, Web of Science, Embase, China Biology Medicine disc, Wanfang Data, China National Knowledge Infrastructure, and China Science and Technology Journal databases from inception to 13 April 2022. Eligible studies included randomized controlled trials of people with lung cancer receiving mindfulness-based interventions reporting on the outcomes of anxiety, depression, and fatigue. Two researchers independently reviewed the abstracts and full texts, extracted the data and assessed the risk of bias independently by using the Cochrane 'Risk of bias assessment tool'. The meta-analysis was performed by using Review Manager 5.4, and the effect size was calculated by the standardized mean difference and its 95% confidence interval. RESULTS: The systematic review included 25 studies (2420 participants), whereas the meta-analysis included 18 studies (1731 participants). Mindfulness-based interventions significantly decreased levels of anxiety [standardized mean difference = -1.15, 95% confidence interval (-1.36, -0.94), Z = 10.75, P < 0.001], depression [standardized mean difference = -1.04, 95% confidence interval (-1.60, -0.48), Z = 3.66, P < 0.001], and fatigue [standardized mean difference = -1.29, 95% confidence interval (-1.66, -0.91), Z = 6.79, P < 0.001]. The subgroup analysis indicated that programs lasting less than eight weeks in length with structured intervention components (e.g., mindfulness-based stress reduction and mindfulness-based cognitive therapy) and 45 min of daily home practice implemented in patients with advanced stage lung cancer showed better effects than programs lasting more than eight weeks in length with less structured components and more than 45 min of daily home practice implemented in patients with mixed stage lung cancer. The overall quality of the evidence was low due to the lack of allocation concealment and blinding and the high risk of bias in most studies (80%). CONCLUSIONS: Mindfulness-based interventions might be effective in reducing anxiety, depression, and fatigue in people with lung cancer. However, we cannot draw definitive conclusions because the overall quality of the evidence was low. More rigorous studies are needed to confirm the effectiveness and examine which intervention components may be most effective for improved outcomes.

Valproic Acid and Lithium Meditate Anti-Inflammatory Effects by Differentially Modulating Dendritic Cell Differentiation and Function.

Valproic acid (VPA), with inhibition activity mainly toward histone deacetylase (HDAC) and Glycogen Synthase Kinase (GSK)-3, and lithium, with inhibition activity mainly toward GSK-3, are both prescribed in clinical as mood-stabilizers and anticonvulsants for the control of bipolar disorder. This study aims to compare the immuno-modulation activities of VPA and lithium, especially on the differentiation and functions of dendritic cells (DC). Our data show that treatment with VPA or lithium effectively alleviated the severity of collagen-induced arthritis triggered by LPS in mice. Both agents reduced the serum level of IL-6 and IL-10 after LPS challenge in mice. VPA and lithium both induce significant down-regulation of group I CD1 expression and secretion of IL-6 during differentiation of human monocyte-derived immature DC, while they differ in the induction of CD83 and CD86 expression, secretion of IL-8, IL-10, and TNF-α. Upon stimulation of immature DC with LPS, VPA, and lithium both reduced the secretion of IL-6 and TNF-α. However, only lithium significantly increased the production of IL-10, while VPA increased the production of IL-8 but substantially reduce the secretion of IL-10 and IL-23. Treatment with VPA resulted in a reduced capacity of LPS-stimulated DC to promote the differentiation of T helper 17 cells that are critical in the promotion of inflammatory responses. Taken together, our results suggest that VPA and lithium may differentially modulate inflammation through regulating the capacity of DC to mediate distinct T cell responses, and they may provide a complementary immunomodulatory effects for the treatment of inflammation-related diseases. J. Cell. Physiol. 232: 1176-1186, 2017. © 2016 Wiley Periodicals, Inc.