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Breast cancer is the second leading cancer diagnosed globally and every year about two million new incidences were accounted. Curcuma wenyujin, a rhizome grown abundantly in china and used in various traditional Chinese medicines. Recent times the research on anticancer property of Curcuma wenyujin is extensively on progress and it is proved by many researchers. The major drawback of herbal drugs are their limited bio-availability, to overcome this we formulated a herbal gold nanodrug with Curcuma wenyujin (CW-AuNPs) and examined its anticancer potential against breast cancer cells. The cytotoxic effect of synthesized CW-AuNPs against MDA-MB231/HER2 cell line was inspected by MTT assay and the dosage for further analysis was calculated. The apoptosis triggered by CW-AuNPs was investigated by intracellular ROS and caspases levels in CW-AuNPs treated MDA-MB231/HER2 cell line. Over expression of HER2/neu, oncogene leads to meager prognosis in most of the breast cancer patients. Therefore in the current exploration, we investigated the inhibitory potential of CW-AuNPs against the expression of HER2/neu in breast cancer cell line by immunocytochemical and immunoblotting analysis. Our results of UV-Spec, FTIR, TEM and Atomic force investigation confirms, the synthesized nanodrug CW-AuNPs satisfies the characteristic features of a nanodrug. The results authentically proves that CW-AuNPs possessed the potent anticancer activity, increases ROS in breast cancer cells which in turn inhibits the HER2/neu, key oncogene expression and inhibited the cancer cell proliferation.

Colorectal cancer (CRC) is one of the most common solid tumors worldwide and has an extremely poor prognosis. MicroRNA-429 (miR-429) has been reported to participate in the progression of CRC. However, the pathological mechanisms require further investigation. The aim of the present study was to investigate the association between miR-429 and high mobility group box 3 (HMGB3) in CRC and the associated mechanism. The mRNA expression levels of miR-429 and HMGB3 in 65 paired CRC and adjacent tissues were examined by reverse transcription-quantitative PCR. Furthermore, a dual-luciferase reporter assay was performed to identify the association between miR-429 and HMGB3. Finally, the effects of miR-429 and HMGB3 on the proliferation and apoptosis of CRC cells were detected. As a result, it was identified that miR-429 expression was downregulated and HMGB3 expression was upregulated in CRC tissues compared with in adjacent non-cancer tissues, and the expression levels of miR-429 were negatively associated with those of HMGB3. Notably, HMGB3 was demonstrated to be a direct target of miR-429 by dual-luciferase reporter assay. Furthermore, transfection with a miR-429 mimic significantly inhibited HMGB3 expression and led to decreased proliferation and increased apoptosis of CRC cells. On the other hand, transient overexpression of HMGB3 partially inhibited the antitumor effects of miR-429. To the best of our knowledge, the present study demonstrated for the first time that miR-429 regulated the proliferation and apoptosis of CRC cells via HMGB3, suggesting a specific tumor suppressive function of the miR-429/HMGB3 signaling pathway in CRC.

Background. Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. Methods. Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. Results. Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln ( OR = 1.71 , 95% CI: 1.16-2.52, p = .007 , I 2 = 56.8 % ) and GlnArg ( OR = 1.23 , 95% CI: 1.07-1.40, p = .003 , I 2 = 29.0 % ) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS ( HR = 0.60 , 95% CI: 0.40-0.88) and PFS ( HR = 0.64 , 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73 , 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28 , 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. Conclusion. Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC.

Objective This study intended to explore the molecular mechanism of RUNX3 in inhibiting the process of migration and proliferation of gastric cancer (GC) cells. Methods The overexpressed plasmids of RUNX3 and the interfering siRNA of RUNX3 were transfected into GC cells. Then, qRT-PCR and western blot were performed to identify the expression level of RUNX3 and miR-182 in tumors and adjacent tissues respectively. ChIP and luciferase assay were performed to detect the relationship between RUNX3 and miR-182 as well as miR-182 and HOXA9. Furthermore, EdU assay were used to investigate the proliferation of GC cells, Transwell assay and wound healing assay were utilized to assess cell metastasis. Xenograft mouse model was set to evaluate the proliferation in vivo. Results The results of qRT-PCR and western blot indicated that RUNX3 could regulate the expression of miR-182. RUNX3 can be straightly interacted with the promoter region of miR-182 in accordance with the results of ChIP. Luciferase assay revealed that HOXA9 was the direct target gene of miR-182. In addition, EdU proliferation, wound healing assay and transwell assay showed that miR-182 mimics and HOXA9 siRNA could inhibit the ability of cells proliferation, migration and invasion. The findings of in vivo experiments strongly supported the view that miR-182/HOXA9 was involved in the process of RUNX3-mediated GC tumor growth. Conclusions RUNX3 could impede the ability of GC cells proliferation, migration and invasion by modulating miR-182/HOXA9 pathway.

Background & Aims The secretory protein Slit2 and its receptor Robo1 are believed to regulate cell growth and migration. Here, we aimed to determine whether Slit2-Robo1 signaling mediates the pathogenesis of liver fibrosis. Methods Serum levels of Slit2 in patients with liver fibrosis were determined by ELISA. Liver fibrosis was induced in wild-type (WT), Slit2 transgenic ( Slit2 -Tg) and Robo1 +/− Robo2 +/− double heterozygotes ( Robo1/2 +/− ) mice by carbon tetrachloride (CCl 4 ). The functional contributions of Slit2-Robo1 signaling in liver fibrosis and activation of hepatic stellate cells (HSCs) were investigated using primary mouse HSCs and human HSC cell line LX-2. Results Significantly increased serum Slit2 levels and hepatic expression of Slit2 and Robo1 were observed in patients with liver fibrosis. Compared to WT mice, Slit2 -Tg mice were much more vulnerable to CCl 4 -induced liver injury and more readily develop liver fibrosis. Development of hepatic fibrosis in Slit2 -Tg mice was associated with a stronger hepatic expression of collagen I and α-smooth muscle actin (α-SMA). However, liver injury and hepatic expression of collagen I and α-SMA were attenuated in CCl 4 -treated Robo1/2 +/− mice in response to CCl 4 exposure. In vitro , Robo1 neutralizing antibody R5 and Robo1 siRNA downregulated phosphorylation of Smad2, Smad3, PI3K, and AKT in HSCs independent of TGF-β1. R5 and Robo1 siRNA also inhibited the expression of α-SMA by HSCs. Finally, the protective effect of R5 on the CCl 4 -induced liver injury and fibrosis was further verified in mice. Conclusions Slit2-Robo1 signaling promotes liver injury and fibrosis through activation of HSCs.