Curcumin is the main component of the Chinese herbal plant turmeric, which has been demonstrated to possess antitumor and other pharmacological properties. The aim of the present study was to investigate the effects of curcumin on the viability, migration and apoptosis of human colorectal carcinoma HCT-116 cells, and to explore the underlying molecular mechanisms. In addition, it was investigated whether the antitumor effect of curcumin on HCT-116 cells could match that of the chemotherapeutic drug 5-fluorouracil (5-FU). HCT-116 cells were treated with curcumin (10, 20 and 30 µM) and 5-FU (500 µM), and cell viability and proliferation were detected by Cell Counting Kit-8 and colony formation assays, respectively. The migration and invasion of treated cells were determined using Transwell and carboxyfluorescein succinimidyl amino ester fluorescent labeling assays. Cell cycle distribution and apoptosis rates were detected by flow cytometry. Furthermore, cell morphology changes associated with apoptosis were observed by fluorescence microscopy with acridine orange/ethidium bromide dual staining. To investigate the possible underlying molecular mechanisms, the gene and protein levels of Fas, Fas-associated via death domain (FADD), caspase-8, caspase-3, matrix metalloproteinase (MMP)-9, nuclear factor (NF)-κB, E-cadherin and claudin-3 were detected using quantitative PCR analysis, zymography and western blotting. The results revealed that curcumin markedly inhibited the viability and proliferation of HCT-116 cells in a dose-and time-dependent manner. The migration, aggregation and invasion of HCT-116 cells into the lungs of mice were decreased by curcumin treatment in a dose-dependent manner. S-phase arrest and gradually increased apoptotic rates of HCT-116 cells were observed with increasing curcumin concentrations. Additionally, the mRNA and protein levels of apoptosis-associated proteins (Fas, FADD, caspase-8 and caspase-3) and E-cadherin in HCT-116 cells were upregulated following treatment with curcumin in a dose-dependent manner. By contrast, the expression of migration-associated proteins, including MMP-9, NF-κB and claudin-3, was downregulated with increasing curcumin concentrations. These data suggested that the inhibitory effect of curcumin on HCT-116 cells may match that of 5-FU. Therefore, curcumin induced cell apoptosis and inhibited tumor cell metastasis by regulating the NF-κB signaling pathway, and its therapeutic effect may be comparable to that of 5-FU.

Cisplatin (DDP) is a potent and widely applied chemotherapeutic agent. However, its clinical efficacy for the treatment of liver cancer is limited by adverse effects and the development of resistance. Combinatorial therapy may alleviate these issues. Dihydroartemisinin (DHA) is a first-generation derivative of artemisinin. The effects of DDP on liver cancer when applied in combination with DHA have not previously been studied. Therefore, the present study aimed to investigate the effects of DHA combined with DDP on HepG2 cells and their potential underlying molecular mechanisms. HepG2 cells were treated with different concentrations of DHA and/or DDP. Cell Counting Kit-8 assay was used to assess the cell viability. Cell proliferation and apoptosis were quantified using flow cytometry, acridine orange/ethidium bromide (AO/EB) fluorescent dual staining and the colony formation assay. Cell migration was quantified using the Transwell and wound healing assays. The HepG2 cell protein expression levels of Fas, Fas-associated death domain (FADD), procaspase-3, cleaved caspase-3, pro-caspase-8, cleaved caspase-8, Bax, Bcl-2, E-cadherin and N-cadherin, were detected via western blotting. Gelatin zymography was used to assess the levels of MMP-9 secreted by HepG2 cells into the supernatant. Following combined DHA and DDP treatment, the percentage of apoptotic cells was significantly increased, whereas cell proliferation and migration were significantly reduced, compared with cells treated with DDP only. DHA and DPP in combination significantly inhibited the expression of MMP-9, significantly increased the protein expression levels of Fas, FADD, Bax and E-cadherin, significantly increased the ratio of cleaved caspase-3 and cleaved caspase-8 to their precursor proteins and significantly decreased the protein expression levels of Bcl-2 and N-cadherin. The findings of the present study suggested that, DHA may confer synergistic effects with DDP in potentially promoting apoptosis and inhibiting the epithelial-mesenchymal transition for the treatment of liver cancer.

Background: Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat gastric cancer (GC) which is the third leading cause of cancer-related death around the world.miR-107, a kind of small non-coding RNAs, play a vital role in the occurrence and development of GC. Aim:A network pharmacology-based strategy combined with in vitro and in vivo experiment were employed to investigate the anticancer effect, potential targets, and molecular mechanism of ZJW against GC by miR-107. Methods:Potential targets and signaling pathways of ZJW to treating gastric cancerby miR-107 were determined usingbioinformatics analysis from public databases. miR-107 and its downstream protein expression levels in GC tissues and cell lines were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) or western blot,which were further confirmed by Luciferase reporter assay and Pearson correlation test.The anticancer effect of ZJW in vitro and in vivo were examined by Nude mouse xenograft tumor model and MGC-803 cells. The possible antitumor mechanism of ZJW was studied by using western blot analysis. Results:A total of 33 bioactive ingredients and 147 gene targets of ZJW acting on GC by miR-107 were identified. The miR-107 level was reduced and RUNX1T1 was down-expressed in GC samples.The expression of target was positively correlated with miR-107 in patients with GC.RUNX1T1 was targeted by miR-107.Since overexpression of miR-107 significantly decreased RUNX1T1 expression in MGC-803 cells, and knockdown of miR-107 enhanced RUNX1T1 expression. ZJW inhibited MGC-803 cells proliferation in dose- and time-dependent manner by activating PI3K/AKT/mTOR pathway and arresting the cell cycle in S phase through regulating the expression of Cyclin A, Cyclin B1 and Cyclin E. ZJW suppressed MGC-803 cells migration in dose-dependent manner by increasing E-cadherin expression. ZJW induced MGC-803 cells apoptosis by Fas death receptor and Bcl-2/Bax pathway. Tumor growth was attenuated by ZJW in nude mouse.miR-107 expression was downregulated in ZJW-treated group compared with untreated group, while the protein expression of RUNX1T1 was upregulated. Conclusions: showed significant anti-tumor activity against gastric cancer MGC-803 cells through multiple signaling pathways via miR-107/RUNX1T1 axis both in vitro and in vivo.

Purpose Dihydroartemisinin (DHA), a derivative of artemisinin that is well-known as an antimalarial drug, has been reported to have anti-tumor and anti-angiogenesis effects. However, whether and how it inhibits angiogenesis in breast cancer is poorly understood. In this study, we detected the anti-angiogenesis effect of DHA on breast cancer. Methods Firstly, we detect the anti-angiogenesis effect of DHA on breast cancer in a chick chorioallantois membrane model. Then, we collected the conditioned medium of MDA-MB-231cells used in aortic ring angiogenesis assay, and HUVECs migration and tube formation assay. Finally, we used gelatin zymography, cellular immunofluorescence assay and western blot analysis to study signaling modulators regulated by DHA in MDA-MB-231 cells. Results The results showed that angiogenesis induced by MDA-MB-231 cells was attenuated by DHA. Vessel sprout and tube-formation of vascular endothelial cells were also depressed when cultured with CM from MDA-MB-231 pretreated with DHA. What’s more, the expression, and activities of matrix metalloproteinase 2 and 9 (MMP-2/-9) in MDA-MB-231 cells were downregulated by DHA. Further studies showed that DHA downregulated the expression of p-PI3K, p-AKT, p-ERK, and p-NF-κB proteins in tumor cells. Conclusion DHA was highly efficacious in inhibiting angiogenesis induced by breast cancer cells. The downregulating of MMP-2/9 through inhibiting phosphorylation of PI3K, AKT, and ERK in tumor cells may be the key factors in the inhibitory effect of DHA on angiogenesis.

BackgroundDihydroartemisinin (DHA) is an artemisinin derivative known for its antimalarial properties. It has also shown potential as an anti‐tumor and anti‐angiogenic agent. However, its specific role in inhibiting angiogenesis in breast cancer is not well understood.ObjectivesWe aimed to investigate the anti‐angiogenesis effect of DHA on breast cancer and explore its potential as a therapeutic drug. Our objectives were to assess the impact of DHA on neovascularization induced by MDA‐MB‐231 cells, evaluate its effects on vessel sprout and tube‐formation in vascular endothelial cells, and analyze the expression of key angiogenesis‐related proteins.MethodsUsing a chicken chorioallantoic membrane (CAM) model, we cultured MDA‐MB‐231 cells and treated them with DHA. We assessed neovascularization and cultured vascular endothelial cells with DHA‐treated cell media to evaluate vessel sprout and tube‐formation. Protein expression levels of VEGF, MMP‐2, and MMP‐9 were analyzed using Western blotting.ResultsDHA significantly attenuated neovascularization induced by MDA‐MB‐231 cells. It also suppressed vessel sprout and tube‐formation of HUVEC cells when exposed to DHA‐treated cell media. Furthermore, DHA downregulated the expression of VEGF, MMP‐2, and MMP‐9 proteins. Mechanistically, DHA inhibited the phosphorylation of PI3K, AKT, ERK, and NF‐κB proteins in tumor cells.ConclusionsOur study provides evidence of the inhibitory effect of DHA on breast cancer angiogenesis. These findings support the potential of DHA as an anti‐breast cancer drug and warrant further investigation for its therapeutic applications.