Lentivirus‐Mediated Small Interfering RNA Targeting VEGF‐C Inhibited Tumor Lymphangiogenesis and Growth in Breast Carcinoma

Guo, Bin; Zhang, Yafang; Luo, Guoqing; Li, Lichun; Zhang, Jianguo

doi:10.1002/ar.20893

Cited by 20 publications

(14 citation statements)

References 31 publications

(35 reference statements)

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“…This immunocompetent BALB/c mouse model mimics the sequential stages of progression of human disease and reproduces the pattern of dissemination observed in patients (37,38). It was observed that intratumoral administration of VEGF-C siRNA significantly suppressed solid tumor growth, which was consistent with the conclusions of Xu et al (39) and Guo et al (40), who transfected VEGF-C siRNA into human breast cancer cells in vitro and in vivo by ultrasound-mediated or lentivirus-mediated methods, respectively. The current study also demonstrated that intratumoral administration of VEGF-C siRNA significantly increased the apoptotic rate of cells in tumor tissue.…”

Section: Discussionsupporting

confidence: 89%

RNAi-mediated gene silencing of vascular endothelial growth factor C suppresses growth and induces apoptosis in mouse breast cancer in vitro and in vivo

Liu

Xue

et al. 2016

Oncology Letters

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Vascular endothelial cell growth factor (VEGF)-C promotes tumorigenesis by allowing lymph node metastasis and lymphangiogenesis, among other actions. RNA interference (RNAi) is a novel technique for suppressing target gene expression and may increase the effectiveness of cancer treatments. The present study assessed the influence of VEGF-C RNAi on the apoptosis and proliferation of mouse breast cancer cells in vitro and in vivo. A total of three pairs of small interfering RNA (siRNA) targeting mouse VEGF-C were designed and synthesized prior to transfection into 4T1 cells via a liposomal approach. Reverse transcription polymerase chain reaction, western blot analysis, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Hoechst 33258 staining and flow cytometry were performed in vitro to analyze VEGF-C expression, cleaved caspase-3 protein expression and 4T1 cell proliferation and apoptosis. Experiments were also conducted in vivo on BALB/c mice with breast cancer. Tumor weight and volume were measured and the number of apoptotic cells in tumor tissues was assessed by a TUNEL assay. Immunohistochemical assays and an enzyme-linked immunosorbent assay were used to measure the expression of VEGF-C in tumor tissues. The results demonstrated that the three pairs of siRNA, particularly siV2, significantly reduced VEGF-C mRNA and protein levels in 4T1 cells. siV2 was deemed to be the most efficient siRNA and therefore was selected to be used in subsequent experiments. Furthermore, in vitro studies indicated that VEGF-C RNAi significantly decreased cell growth, induced apoptosis and upregulated the expression of cleaved caspase-3 protein. Tumor weight and volume in breast cancer in vivo models was reduced by the intratumoral injection of siV2. Antitumor efficacy was associated with decreased VEGF-C expression and increased induction of apoptosis. The present study therefore indicated that VEGF-C RNAi inhibited mouse breast cancer growth in vitro and in vivo and that it may be a novel targeted therapy for breast cancer.

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Section: Discussionsupporting

confidence: 89%

RNAi-mediated gene silencing of vascular endothelial growth factor C suppresses growth and induces apoptosis in mouse breast cancer in vitro and in vivo

Liu

Xue

et al. 2016

Oncology Letters

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“…Researchers have focused on hot-spots of treating carcinoma by inhibition or destroying of tumor lymphatic tube formation early, i.e., lymphangiogenesis (9,10,18). These lymphangiogenic inhibitors such as deguelin, endostar, silencing Id-1, liposomal honokiol, mF4-31C1, Ki23057, sVEGFR3-Ig, VEGFR31-Ig, artemisinin, etodolac, MMI270, CSDA and AZM475271 have been reported as adjuvant anti-lymphangiogenic and anti-tumor drugs against some metastatic cancers in experimental and in clinical setting (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). NCTD has been reported to possess potent anti-angiogenesis and antitumor properties in several cell lines and tumor models (11)(12)(13)(14)(15)(16)(38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 98%

“…chemical technique via CD 31 , podoplanin and Lyve1. Tissue culture flasks were peridiumed with fibronectin (1 mg/ml; Chemicon, USA).…”

Section: Suppression Of Lymphangiogenesis In Human Lymphatic Endothelmentioning

confidence: 99%

Suppression of lymphangiogenesis in human lymphatic endothelial cells by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 with norcantharidin

Liu¹,

Qiu²,

Yuan³

et al. 2012

International Journal of Oncology

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Lymph node metastasis of tumors is a crucial early step in the metastatic process. Tumor lymphangiogenesis plays an important role in promoting tumor metastasis to regional lymph nodes. Norcantharidin (NCTD) has been reported to possess potent anti-angiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor-associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we investigated the effect of NCTD on proliferation, apoptosis, migration, invasion and the lymphatic tube formation, lymphangiogenesis, of human lymphatic endothelial cells (HLECs) in vitro by MTT, proliferation assay, Hoechst staining and flow cytometry, scraping line method, Matrigel invasion assay, inverted or fluorescence microscope and transmission electron microscope. Moreover, the underlying mechanisms, such as VEGF-C, VEGF-D, VEGFR-3 at protein and mRNA levels in lymphangiogenesis using 3-dimensional (3-D) culture of HLECs were measured by immunohistochemistry, western blotting and real-time polymerase chain reaction (RT-PCR). It was shown that NCTD inhibited proliferation, migration, invasion and lymphatic tube formation (forming-lymphatic and/or formed-lymphatic) of HLECs, induced HLEC apoptosis (all P<0.01) significantly, in a dose- and time-dependent manner (IC50 6.8 µg/ml); and downregulated the expression of VEGF-C, VEGF-D and VEGFR-3 at protein or/and mRNA levels (P<0.01) in HLEC lymphatic tube formation. Thus, we identified for the first time that NCTD inhibited HLEC lymphangiogenesis by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 in vitro. The present findings may be of importance to explore the therapeutical target or strategy of NCTD for tumor lymphangiogenesis and lymphatic metastasis.

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“…VEGFs are known to be one group comprising the strongest angiogenic and lymphangiogenic factors during epithelial carcinogenesis and tumour metastasis 62 63. Shao et al 64 determined the protein expression level of VEGF in 59 tongue cancers and 10 normal mucosas, indicating that the overexpression of VEGF protein might contribute to tumour angiogenesis and have prognostic value in tongue cancer.…”

Section: Cytokinementioning

confidence: 99%

Biomarkers in tongue cancer: understanding the molecular basis and their clinical implications

Zheng

Li²,

Tang³

et al. 2010

Postgraduate Medical Journal

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Tongue cancer, one of the most common malignant cancers of the oral cavity, still affects human health worldwide due to its disappointing survival rates, despite significant developments in its multimodality treatment. The predominant cause of death in patients with tongue cancer is the high occurrence of invasion to surrounding tissues, lymph and distant metastasis, and recurrence. Due to the limited value of conventional predictive and prognostic factors and the uniformity of treatment strategies, several patients are still over- or under-treated, with significantly personal and socioeconomic impact. This review focuses on some promising predictive and prognostic biomarkers of tongue cancer and their actual/potential clinical implications, in order to provide clinicians with useful information for the improvement of early diagnostic/prognostic evaluation and management of patients with tongue cancer.

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Lentivirus‐Mediated Small Interfering RNA Targeting VEGF‐C Inhibited Tumor Lymphangiogenesis and Growth in Breast Carcinoma

Abstract: Lymph node metastasis is a major prognostic factor for patients with breast cancer.

Cited by 20 publications

References 31 publications

RNAi-mediated gene silencing of vascular endothelial growth factor C suppresses growth and induces apoptosis in mouse breast cancer in vitro and in vivo

RNAi-mediated gene silencing of vascular endothelial growth factor C suppresses growth and induces apoptosis in mouse breast cancer in vitro and in vivo

Suppression of lymphangiogenesis in human lymphatic endothelial cells by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 with norcantharidin

Biomarkers in tongue cancer: understanding the molecular basis and their clinical implications

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