• 제목/요약/키워드: anti-invasive

검색결과 136건 처리시간 0.032초

FNC, a Novel Nucleoside Analogue, Blocks Invasion of Aggressive Non-Hodgkin Lymphoma Cell Lines Via Inhibition of the Wnt/β-Catenin Signaling Pathway

  • Zhang, Yan;Wang, Chen-Ping;Ding, Xi-Xi;Wang, Ning;Ma, Fang;Jiang, Jin-Hua;Wang, Qing-Duan;Chang, Jun-Biao
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권16호
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    • pp.6829-6835
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    • 2014
  • Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

인체유방암세포의 tight junction 기능 조절을 통한 genistein의 암세포 침윤 억제 효과 (Anti-invasive Activity of Human Breast Carcinoma Cells by Genistein through Modulation of Tight Junction Function)

  • 김성옥;정영기;최영현
    • 생명과학회지
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    • 제19권9호
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    • pp.1200-1208
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    • 2009
  • Tight junctions (TJs)은 인접된 세포 사이의 전해질 및 거대분자 확산 조절에 관여하는 paracellular permeability의 장벽 역할을 한다. 본 연구에서는 MCF-7 및 MDA-MB-231 인체유방암세포에서 대두의 대표적인 생리활성물인 genistein에 의한 암세포의 침윤 억제에서 TJs의 견고성 및 투과성과의 연관성을 조사하였다. 본 연구의 결과에 의하면 genistein에 의한 유방암세포의 증식 억제, 암세포 이동성의 저하 및 침윤성의 억제는 TJs의 증가된 견고성과 연관이 있었으며, 이를 transepithelial electrical resistance의 증가 및 paracellular permeability의 감소로 확인하였다. Genistein은 두 유방암세포에서 TJs의 주요 조절 단백질로서 paracellular transport 조절에 중요한 역할을 하는 claudin-3 및 claudin-4의 발현을 억제시켰다. 그리고 genistein은 암세포의 전이 조절 관련 유전자들인 like growth factor-1 receptor 및 snail의 발현을 억제하였으며, thrombospondin-1 및 E-cadherin의 발현은 증가시켰다. 또한 small interfering RNA를 이용하여 genistein의 유방암세포의 침윤 억제에서 claudin-3단백질의 중요성을 확인하였다. 결론적으로 genistein이 TJs의 견고성 증가를 통하여 암세포의 침윤성을 억제할 수 있었으며, 이 과정에서 아마도 claudin 단백질의 발현 증가가 중요한 역할을 하고 있음을 알 수 있었다. 본 연구의 결과는 genistein이 종양 전이억제를 효과적으로 차단할 수 있음을 보여주는 것이다.

Anti-Proliferative Effects of Hesa-A on Human Cancer Cells with Different Metastatic Potential

  • Jahanban-Esfahlan, Rana;Abasi, Mozhgan;Sani, Hakimeh Moghaddas;Abbasi, Mehran Mesgari;Akbarzadeh, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권16호
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    • pp.6963-6966
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    • 2015
  • Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of $100{\mu}/ml$, $200{\mu}g/ml$, $300{\mu}g/ml$ and $400{\mu}g/ml$. MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$). At the lower dose ($100{\mu}g/ml$), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential.

Expression of Bax and Bcl-2 in Tumour Cells and Blood Vessels of Breast Cancer and their Association with Angiogenesis and Hormonal Receptors

  • Jaafar, Hasnan;Abdullah, Suhaila;Murtey, Mogana Das;Idris, Fauziah M.
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.3857-3862
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    • 2012
  • A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

Upregulated Myc Expression in N-Methyl Nitrosourea (MNU)-induced Rat Mammary Tumours

  • Barathidasan, Rajamani;Pawaiya, Rajveer Singh;Rai, Ram Bahal;Dhama, Kuldeep
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권8호
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    • pp.4883-4889
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    • 2013
  • Background: The most common incident cancer and cause of cancer-related deaths in women is breast cancer. The Myc gene is upregulated in many cancer types including breast cancer, and it is considered as a potential anti-cancer drug target. The present study was conducted to evaluate the Myc (gene and protein) expression pattern in an experimental mammary tumour model in rats. Materials and Methods: Thirty six Sprague Dawley rats were divided into: Experimental group (26 animals), which received the chemical carcinogen N-methyl nitrosourea (MNU) and a control group (10 animals), which received vehicle only. c-Myc oncoprotein and its mRNA expression pattern were evaluated using immunohistochemistry (IHC) and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal rat mammary tissue and mammary tumours. The rat glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as internal control for semi-quantitative RT-PCR. Results: Histopathological examination of mammary tissues and tumours from MNU treated animals revealed the presence of premalignant lesions, benign tumours, in situ carcinomas and invasive carcinomas. Immunohistochemical evaluation of tumour tissues showed upregulation and heterogeneous cellular localization of c-Myc oncoprotein. The expression levels of c-Myc oncoprotein were significantly elevated (75-91%) in all the tumours. Semi-quantitative RT-PCR revealed increased expression of c-Myc mRNA in mammary tumours compared to normal mammary tissues. Conclusions: Further large-scale investigation study is needed to adopt this experimental rat mammary tumour model as an in vivo model to study anti-cancer strategies directed against Myc or its downstream partners at the transcriptional or post-transcriptional level.

국내 임상 분리주 Streptococcus pneumoniae KNIH1156으로부터 PspA 단백 항원의 정제 및 면역원성 확인 (The Purification and Immunogenicity of Pneumococcal Surface Protein (PspA) from Invasive Streptococcus pneumoniae KNIH1156 Isolated in Korea)

  • 정경석;배송미
    • 미생물학회지
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    • 제38권1호
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    • pp.38-44
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    • 2002
  • 국내 분리 침습성 균주중선별된 S. pneumoniae KNIH1156 (type 19F)으로부터 페렴구균의 병원성 인자이며 항원학적으로 다양한 표면단백항원인 pneumococcal surface protein A (PspA)를 분리${\cdot}$정제하였다. 폐렴구균을 CDM-ET배지에서 배양하게 되면 배지내로 PspA가 방출된다는 점과 PspA가 인간의 lactoferrin에 특이적으로 결합한다는 사실을 이용하여 CDM-ET 배지에서 S. pneumoniae KNIH1156 을 배양한 후 배양액을 농축하여 lactoferrinaffinity chromatography에 통과시켜 PspA를 분리, 정제하였다. 정제 후 anti-PspA antiserum으로 PspA를 확인하여 순수분리, 정제되었음을 확인하였으며 또한 인간의 lactoferrin과의 결합능력을 유지하고 있음을 확인하였다. 순수하게 분리하여 정제된 PspA의 면역원성을 확인하기 위하여 ICR mice에 욕강주사하였을 때 $LD_{50}$$1{\times}10^{7.5}$ CFU/ml께서 $1{\times}10^{10}$ CFU/ml로 약 500배 중가함을 관찰하였다. 따라서 본 실험에서S. pneumoniae KNIH1156 으로부터 분리${\cdot}$ 정제한 PspA가 면역원성과 방어능을 가지고 있음을 확인할 수 있었다.

구강편평세포암종에서 신생혈관화와 기저막침습에 미치는 제니스타인의 효과 (THE EFFECT OF GENISTEIN IN ORAL SQUAMOUS CELL CARCINOMA WITH RESPECT TO THE ANGIOGENESIS AND BASEMENT MEMBRANE INVASION)

  • 김용훈;윤필영;명훈;김명진
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제28권6호
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    • pp.434-439
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    • 2002
  • Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. OSCC generally has a poor prognosis due to its tendency towards a local invasion and subsequent metastasis, which is mediated by multiple proteolytic enzymes and angiogenesis. Soy products contain high levels of isoflavonoids, including the tyrosine kinase inhibitor, genistein, which has been identified as a potent inhibitor of cell proliferation and in vitro angiogenesis. The purpose of this in vitro study is to evaluate the anti-cancer effect of genistein with respect to the angiogenesis and basement membrane invasion in OSCC. The highly invasive OSCC cell line, HSC-3 cells were cultured in the presence of $10{\mu}M$ genistein for 24h. To evaluate the effects of genistein on the invasiveness and the gelatinolytic activity, in vitro invasion assay and zymography were performed. In order to evaluate the effect on the VEGF and bFGF mRNA expression, RT-PCR and northern hybridization reaction, and chemiluminescence detection were applied. The in vitro invasion assay showed that the genistein treatment reduced the cellular invasion through the artificial basement membrane and significant difference between the control group and the genistein treated group was shown in MMP-2 activity. Especially, the 62 kDa activated form of MMP-2 in the control group was 1.8 times higher than that in the genistein treated group. The results of the northern blot analyses indicated that VEGF mRNA expression in the genistein treated group was significantly down regulated. This study showed that genistein inhibits angiogenesis and reduces basement membrane invasion in OSCC. It seems to support the possibility of genistein as an anti-cancer agent.

적송엽(赤松葉) 함유 한방화장품(韓方化粧品)이 인체(人體) 피부(皮膚) 노화(老化)에 미치는 영향(影響) 연구 (The Anti-aging Effects of the Cosmetic Products Containing the Needles of Red Pine on Human Skin)

  • 김은주;안성연;남개원;이해광;문성준;김용민;오명숙;김남수;장이섭;박성규
    • 대한본초학회지
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    • 제21권1호
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    • pp.25-31
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    • 2006
  • Objectives : We investigated the aniti-aging effects of the cosmetic products with Pinus densiflora on human skin by using non-invasive instruments. Methods : We made cosmetic products containing the extract of the needles of red pine, and measured physiological effects such as skin wrinkles, clarity, evenness, lifting, corneocyte exfoliation after volunteers applied the cosmetic products for 8 weeks. Results : We observed a skin lifting effect and a decrease in corneocytes amount after using the cosmetic products for 4 weeks. And the wrinkles, evenness and clarity of face skin improved significantly. Conclusion : We concluded that the cosmetic products containing the extract of the needles of reel pine had an anti-aging effect on the human face skin.

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주성분 분석을 이용한 펄스형 전자기장 자극을 통해 DNCB로 유발된 아토피성 피부염의 개선 효과 분석 (Evaluation of Anti-Inflammatory Effect of Pulsed Electromagnetic Field on DNCB-Induced Atopic Dermatitis Using Principal Component Analysis)

  • 이지영;김준영;이예린;김고은;이용흠;양세정
    • 대한의용생체공학회:의공학회지
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    • 제42권3호
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    • pp.94-99
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    • 2021
  • Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by itchy and age-dependent lesions. Previous studies have shown that pulsed electromagnetic field (PEMF) significantly improved chronic ulcers and ununited fractures, providing an evidence for the application of PEMF in resolving inflammation caused by AD. This study investigated the anti-inflammatory effect of PEMF on DNCB-induced AD in animal models. Five male hairless mice (6 weeks old) per group were assigned to a normal group, a sham group, and two PEMF groups (15Hz, 75Hz). Mice were treated with 2,4-Dinitrochlorobenzene (DNCB) to induce uniform AD among all groups excluding a normal group. To examine the inflammatory progress and the improvement of AD after the PEMF stimulation, images are taken with various cameras for non-invasive evaluation and the results are expressed using principal component analysis (PCA) for visualization. The results of this study demonstrated that PEMF effectively improved skin lesions without the use of drugs.

Sanghuangporus sanghuang extract inhibits the proliferation and invasion of lung cancer cells in vitro and in vivo

  • Weike Wang;Jiling Song;Na Lu;Jing Yan;Guanping Chen
    • Nutrition Research and Practice
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    • 제17권6호
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    • pp.1070-1083
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    • 2023
  • BACKGROUND/OBJECTIVES: Sanghuangporus sanghuang (SS) has various medicinal effects, including anti-inflammation and anticancer activities. Despite the extensive research on SS, its molecular mechanisms of action on lung cancer are unclear. This study examined the impact of an SS alcohol extract (SAE) on lung cancer using in vitro and in vivo models. MATERIALS/METHODS: Different concentrations of SAE were used to culture lung cancer cells (A549 and H1650). A cell counting kit-8 assay was used to detect the survival ability of A549 and H1650 cells. A scratch assay and transwell cell invasion assay were used to detect the migration rate and invasive ability of SAE. Western blot analysis was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), cyclin D1, cyclin-dependent kinases 4 (CDK4), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Lung cancer xenograft mice were used to detect the inhibiting ability of SAE in vivo. Hematoxylin and eosin staining and immunohistochemistry were used to detect the effect of SAE on the structural changes to the tumor and the expression of Bcl-2, Bax, cyclin D1, CDK4, STAT3, and p-STAT3 in lung cancer xenograft mice. RESULTS: SAE could inhibit lung cancer proliferation significantly in vitro and in vivo without cytotoxicity. SAE suppressed the viability, migration, and invasion of lung cancer cells in a dose and time-dependent manner. The SAE treatment significantly decreased the proapoptotic Bcl-2/Bax ratio and the expression of pro-proliferative proteins Cyclin D1 and CDK4 in vitro and in vivo. Furthermore, SAE also inhibited STAT3 expression. CONCLUSIONS: SAE reduced the cell viability and suppressed cell migration and invasion in human lung cancer cells. Moreover, SAE also exhibited anti-proliferation effects in vivo. Therefore, SAE may have benefits in cancer therapy.