Elucidation of the effect of plumbagin on the metastatic potential of B16F10 murine melanoma cells via MAPK signalling pathway.
白花丹苷通过 MAPK 信号通路对 B16F10 鼠黑色素瘤细胞转移潜能影响的阐明。
- 作者列表："Alem FZ","Bejaoui M","Villareal MO","Rhourri-Frih B","Isoda H
:Melanoma is the most dangerous form of skin cancer with a very poor prognosis. Melanoma develops when unrepaired DNA damage causes to skin cells to multiply and form malignant tumors. The current therapy is limited by the highly ability of this disease to metastasize rapidly. Plumbagin is a naphthoquinone (5-hydroxy-2-methyl-1, 4-naphthoquinone), isolated from the roots of medicinal plant Plumbago zeylanica, and it is widely present in Lawsonia inermis L. It has been shown that plumbagin has an anti-proliferative and anti-invasive activities in various cancer cell lines; however, the anti-cancer and anti-metastatic effects of plumbagin are largely unknown against melanoma cells. In this study, we evaluated the effect of plumbagin on B16F10 murine melanoma cells . Plumbagin decreased B16F10 cell viability as well as the cell migration, adhesion, and invasion. The molecular mechanism was studied, and plumbagin downregulated genes relevant in MAPK pathway, matrix metalloproteinases (MMP's), and cell adhesion. Furthermore, plumbagin elevated the expression of apoptosis and tumors suppressor genes, and genes significant in reactive oxygen species (ROS) response. Taken together, our findings suggest that plumbagin has an anti-invasion and anti-metastasis effect on melanoma cancer cells by acting on MAPK pathway and its related genes.
: 黑色素瘤是最危险的皮肤癌，预后极差。当未修复的 DNA 损伤导致皮肤细胞增殖并形成恶性肿瘤时，黑色素瘤就会发展。目前的治疗受到这种疾病快速转移的高度能力的限制。白花丹素是一种萘醌 (5-羟基-2-甲基-1,4-萘醌)，从药用植物白花丹的根部分离得到，广泛存在于 Lawsonia inermis L 中。研究表明，白花丹素在各种癌细胞系中具有抗增殖和侵袭活性; 然而, 白花丹素对黑色素瘤细胞的抗癌和抗转移作用在很大程度上是未知的。在本研究中，我们评价了白花丹素对 B16F10 鼠黑色素瘤细胞的影响。白花丹素降低 B16F10 细胞活力以及细胞迁移、粘附和侵袭。对其分子机制进行了研究，并对 MAPK 通路、基质金属蛋白酶 (MMP) 和细胞粘附相关基因进行了研究。此外，白花丹素能提高细胞凋亡和肿瘤抑制基因的表达，以及活性氧 (ROS) 反应中显著的基因。总之，我们的研究结果表明，白花丹苷通过作用于 MAPK 通路及其相关基因，对黑色素瘤癌细胞具有抗侵袭和抗转移作用。
METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.
METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.