• Journal of Digestive Cancer Research
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• v.6 no.2
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• pp.45-49
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• 2018

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the world. Although the long-term outcome of patients with metastatic CRC is still poor, target therapy including anti EGFR agents and anti VEGF agents and immunotherapy including anti PD-1 antibody and anti CTLA-4 antibody have shown clinical benefits in the treatment of patient with metastatic CRC. In the future, the personalized treatment strategy based on the clinical characteristics and biologic features of patients with metastatic CRC will be necessary. In this review, we summarized the mechanisms and clinical evidences of target therapy and immunotherapy, and the guideline of clinical practice in patients with metastatic CRC.

• Archives of Pharmacal Research
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• v.20 no.6
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• pp.539-544
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• 1997

Anti-metastatic activities of IH901, an intestinal bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo. Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT 1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

• BMB Reports
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• v.56 no.7
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• pp.410-415
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• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1011-1015
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• 2005

Antitumor and anti-metastatic effects of mineral powder(MP) were studied. In the present study, MP did not exhibit the any cytotoxic activity against leukemic cells such as L1210 and U937 tumor cell lines in vitro. Also, MP did not exhibit the any cytotoxic activity against solid cells such as A549 and B16-BL6 tumor cell lines in vitro. However, in vivo, MP exhibit a significant antitumor activity in BDF1 mice bearing Lewis lung carcinoma cells(LLC) with inhibition rates of 46 and $23\%$ at 200 and 100 mg/kg/day, respectively. Furthermore, in pulmonary colonization assay, MP exhibit the inhibitory effect of tumor metastasis. From these results, it was concluded that MP had antitumor and anti-metastatic activity suggesting its application for the prevention and treatment of cancer.

• Natural Product Sciences
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• v.18 no.2
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• pp.89-96
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• 2012

Ligularia stenocephala has been used as a traditional medicine for the treatment of asthma, arthritis, jaundice, and hyperpiesia. In this study, we investigated the anti-metastatic and hypnotic effects of the methanolic extract of L. stenocephala (MLS). Gelatin zymographic analysis revealed that MLS suppresses matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in B16F10 cells. The gene expressions of MMPs were also down-regulated by MLS treatment in a dose-dependent manner. In addition, cancer cell invasion and migration were attenuated by MLS via suppression of NF-${\kappa}B$ activation. The in vivo lung metastasis of B16F10 melanoma cells was also inhibited by the treatment of MLS. These findings show that MLS has anti-metastatic properties, and, therefore, it might be applicable as a valuable anti-metastatic agent.

• Natural Product Sciences
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• v.17 no.2
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• pp.135-141
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• 2011

Celastrus orbiculatus has been widely used as a traditional medicine for the treatment of many diseases including rheumatoid arthritis and odontalgia. In the present study, anti-metastatic activity of a methanolic extract from C. orbiculatus (MCO) was studied. A gelatin zymographic assay revealed that MCO has potent inhibitory effects on MMP-2 and MMP-9 activities in B16F10 melanoma cells. Moreover, MCO attenuated MMP expression via down-regulation of NF-${\kappa}$B translocation to the nucleus. Melanoma cell migration and invasion were also down-regulated by MCO. In addition, MCO significantly suppressed lung metastasis in an in vivo model. These results strongly suggest that MCO may possibly be used as a valuable anti-metastatic agent for cancer treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1470-1474
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• 2008

This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.968-974
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• 2011

Saussurea lappa Clarke is a well-known transitional medicine in Asia including Korea, China and Japan. It has been reported that Clarke has diverse effects such as anti-viral, anti-inflammatory, anti-cancer in human gastric cells and human prostate cancer cells. However, the anti-cancer effects and the mechanism of actions of Saussurea lappa Clarke are still unknown in breast cancer. In this study, we observed that Saussurea lappa Clarke inhibits the cell growth in a dose- and time-dependent manner in highly-metastatic MDA-MB-231 breast cancer cells. In order to examine whether Saussurea lappa Clarke suppresses cell growth inducing apoptosis cell death or cell cycle arrest, we analyzed DNA contents and cell cycle distribution using a flow cytometer and western blotting in MDA-MB-231 cells. We suggest that Saussurea lappa Clarke dose not induced apoptosis and induced G2/M phase cell cycle arrest. Moreover, Saussurea lappa Clarke also decreased the expression level of metastasis-angiogenesis releated protein such as VEGF. However, dose not changed the expression level of metastasis related protease MMP-1 in highly-metastatic MDA-MB-231 breast cancer cells. Therefore, Saussurea lappa Clarke might be good and useful chemotherapy agent highly-metastatic breast cancer patients.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

• Journal of Microbiology and Biotechnology
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• v.25 no.12
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• pp.1997-2006
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• 2015

Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.