scholarly journals Anlotinib induces tumor blood vessel normalization to strengthen the anticancer effect of radiotherapy on esophageal cancer by inhibiting EphA2

2021 ◽  
Author(s):  
Weiguo Zhu ◽  
Jing Huang ◽  
Zhenlin Gu ◽  
Jiasheng Huang ◽  
Yingying Xu ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Tumor Growth ◽  
Migration And Invasion ◽  
Anticancer Effect ◽  
Mediated Effects ◽  
Vessel Normalization ◽  
Ec Cells ◽  
Anti Tumor Activity

Abstract Background Anlotinib has anti-tumor activity in diverse solid tumors. Given that, our study was designed to unearth the mechanism of Anlotinib in radioresistant esophageal cancer (EC) cells by modulating Ephrin type-A receptor 2 (EphA2). Methods EC cells (TE-1 and KYSE-150) were induced to radioresistant EC cells (TE-1R and KYSE-150R). EphA2 expression in TE-1R and KYSE-150R cells was measured. Then, TE-1R and KYSE-150R cells were treated with Anlotinib and/or transfected with the plasmids that altered EphA2 expression. Otherwise, TE-1R and KYSE-150R cells were transfected with si-EphA2 or OE-EphA2 plasmids independently. In vitro experiments were conducted to monitor cell proliferation, angiogenesis, migration and invasion. In vivo experiment was also implemented to observe tumor growth. Results EphA2 expression was raised in TE-1R and KYSE-150R cells. Anlotinib inhibited proliferation, angiogenesis, migration and invasion of TE-1R and KYSE-150R cells in vitro, as well as tumor growth and MVD in vivo. Inhibiting EphA2 enhanced Anlotinib-mediated effects on TE-1R and KYSE-150R cells. Down-regulating EphA2 restrained proliferation, angiogenesis, migration and invasion of TE-1R and KYSE-150R cells. Conclusion It is concluded that Anlotinib suppresses EC development under radiotherapy by inhibiting EphA2, providing another perspective to overcome radioresistance in EC.

scholarly journals RAB11A mediates the proliferation and motility of esophageal cancer cells via WNT signaling pathway

2020 ◽  
Author(s):  
Danyi Zhao ◽  
Bing Wang ◽  
Huawei Chen
Keyword(s):  
Esophageal Cancer ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Small Gtpases ◽  
Migration And Invasion ◽  
Cellular Functions ◽  
In Vivo Experiments ◽  
Ec Cells

Esophageal cancer (EC) recently has become a common malignancy of digestive system worldwide. RAB11A is a critical member of the small GTPases superfamily and was reported to affect a variety of cellular functions. However, its potential effects on EC progression and the specific regulatory mechanisms are still unclear. In this study, RAB11A was upregulated in human EC tissues and cells and predicted poor diagnosis. RAB11A expression was correlated with clinical-pathological features including pTNM stage (P=0.001*) and recurrence (P=0.000**) in patients with EC. Furthermore, RAB11A knockdown decreased the proliferation, migration, and invasion of EC cells via WNT pathway in vitro. Subsequently, the in vivo experiments confirmed that RAB11A contributed to EC tumor growth via WNT pathway. Therefore, these results provided evidence showing that RAB11A could promote the progression of EC via WNT pathway and might serve as a promising therapeutic target for EC treatment.

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

scholarly journals HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Chun Cheng ◽  
Jun Yang ◽  
Si-Wei Li ◽  
Guofu Huang ◽  
Chenxi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Therapeutic Target ◽  
Histone Deacetylases ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractHistone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

scholarly journals A Novel Bispecific Antibody Targeting EGFR and VEGFR2 Is Effective against Triple Negative Breast Cancer via Multiple Mechanisms of Action

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1027
Author(s):  
Nishant Mohan ◽  
Xiao Luo ◽  
Yi Shen ◽  
Zachary Olson ◽  
Atul Agrawal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Growth ◽  
Mechanisms Of Action ◽  
Breast Cancers ◽  
Single Chain ◽  
Cancer Cell Growth ◽  
Anti Tumor Activity ◽  
Enhance Tumor Growth

Both EGFR and VEGFR2 frequently overexpress in TNBC and cooperate with each other in autocrine and paracrine manner to enhance tumor growth and angiogenesis. Therapeutic mAbs targeting EGFR (cetuximab) and VEGFR2 (ramucirumab) are approved by FDA for numerous cancer indications, but none of them are approved to treat breast cancers. TNBC cells secrete VEGF-A, which mediates angiogenesis on endothelial cells in a paracrine fashion, as well as promotes cancer cell growth in autocrine manner. To disrupt autocrine/paracrine loop in TNBC models in addition to mediating anti-EGFR tumor growth signaling and anti-VEGFR2 angiogenic pathway, we generated a BsAb co-targeting EGFR and VEGFR2 (designated as anti-EGFR/VEGFR2 BsAb), using publicly available sequences in which cetuximab IgG backbone is connected to the single chain variable fragment (scFv) of ramucirumab via a glycine linker. Physiochemical characterization data shows that anti-EGFR/VEGFR2 BsAb binds to both EGFR and VEGFR2 in a similar binding affinity comparable to parental antibodies. Anti-EGFR/VEGFR2 BsAb demonstrates in vitro and in vivo anti-tumor activity in TNBC models. Mechanistically, anti-EGFR/VEGFR2 BsAb not only directly inhibits both EGFR and VEGFR2 in TNBC cells but also disrupts autocrine mechanism in TNBC xenograft mouse model. Furthermore, anti-EGFR/VEGFR2 BsAb inhibits ligand-induced activation of VEGFR2 and blocks paracrine pathway mediated by VEGF secreted from TNBC cells in endothelial cells. Collectively, our novel findings demonstrate that anti-EGFR/VEGFR2 BsAb inhibits tumor growth via multiple mechanisms of action and warrants further investigation as a targeted antibody therapeutic for the treatment of TNBC.

scholarly journals LY2157299 Monohydrate, a TGF-βR1 Inhibitor, Suppresses Tumor Growth and Ascites Development in Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 260 ◽  
Author(s):  
Qing Zhang ◽  
Xiaonan Hou ◽  
Bradley Evans ◽  
Jamison VanBlaricom ◽  
Saravut Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cell Lines ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Migration And Invasion ◽  
Ascites Formation ◽  
Tgf Β1

Transforming growth factor beta (TGF-β) signaling has pleiotropic functions regulating cancer initiation, development, and metastasis, and also plays important roles in the interaction between stromal and cancer cells, making the pathway a potential therapeutic target. LY2157299 monohydrate (LY), an inhibitor of TGF-β receptor I (TGFBRI), was examined for its ability to inhibit ovarian cancer (OC) growth both in high-grade serous ovarian cancer (HGSOC) cell lines and xenograft models. Immunohistochemistry, qRT-PCR, and Western blot were performed to study the effect of LY treatment on expression of cancer- and fibroblast-derived genes. Results showed that exposure to TGF-β1 induced phosphorylation of SMAD2 and SMAD3 in all tested OC cell lines, but this induction was suppressed by pretreatment with LY. LY alone inhibited the proliferation, migration, and invasion of HGSOC cells in vitro. TGF-β1-induced fibroblast activation was blocked by LY. LY also delayed tumor growth and suppressed ascites formation in vivo. In addition, independent of tumor inhibition, LY reduces ascites formation in vivo. Using OVCAR8 xenograft specimens we confirmed the inhibitory effect of LY on TGF-β signaling and tumor stromal expression of collagen type XI chain 1 (COL11A1) and versican (VCAN). These observations suggest a role for anti-TGF-β signaling-directed therapy in ovarian cancer.

scholarly journals Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Tao Chen ◽  
Fu-Kuan Zhong
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

scholarly journals Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Zhirong Li ◽  
Xuebo Qin ◽  
Wei Bian ◽  
Yishuai Li ◽  
Baoen Shan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Donor Cells

Abstract Background In recent years, long non-coding RNAs (lncRNAs) are of great importance in development of different types of tumors, while the function of lncRNA ZFAS1 is rarely discussed in esophageal squamous cell carcinoma (ESCC). Therefore, we performed this study to explore the expression of exosomal lncRNA ZFAS1 and its molecular mechanism on ESCC progression. Methods Expression of ZFAS1 and miR-124 in ESCC tissues was detected. LncRNA ZFAS1 was silenced to detect its function in the biological functions of ESCC cells. A stable donor and recipient culture model was established. Eca109 cells transfected with overexpressed and low expressed ZFAS1 plasmid and miR-124 inhibitor labeled by Cy3 were the donor cells, and then co-cultured with recipient cells to observe the transmission of Cy3-ZFAS1 between donor cells and recipient cells. The changes of cell proliferation, apoptosis, invasion, and migration in recipient cells were detected. The in vivo experiment was conducted for verifying the in vitro results. Results LncRNA ZFAS1 was upregulated and miR-124 was down-regulated in ESCC tissues. Silencing of ZFAS1 contributed to suppressed proliferation, migration, invasion and tumor growth in vitro and induced apoptosis of ESCC cells. LncRNA ZFAS1 was considered to be a competing endogenous RNA to regulate miR-124, thereby elevating STAT3 expression. Exosomes shuttled ZFAS1 stimulated proliferation, migration and invasion of ESCC cells and restricted their apoptosis with increased STAT3 and declined miR-124. Furthermore, in vivo experiment suggested that elevated ZFAS1-exo promoted tumor growth in nude mice. Conclusion This study highlights that exosomal ZFAS1 promotes the proliferation, migration and invasion of ESCC cells and inhibits their apoptosis by upregulating STAT3 and downregulating miR-124, thereby resulting in the development of tumorigenesis of ESCC.

scholarly journals LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zheng ◽  
Bowen Zheng ◽  
Xue Meng ◽  
Yuwen Yan ◽  
Jia He ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Ectopic Expression ◽  
Underlying Mechanism ◽  
Tongue Squamous Cell Carcinoma ◽  
Migration And Invasion

Abstract Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.

scholarly journals TRIM33 Overexpression Inhibits the Progression of Clear Cell Renal Cell Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yingkun Xu ◽  
Guangzhen Wu ◽  
Jiayao Zhang ◽  
Jianyi Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mrna Expression ◽  
Wnt Signaling Pathway ◽  
Xenograft Model ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Purpose. To evaluate the expression of tripartite motif-containing 33 (TRIM33) in ccRCC tissues and explore the biological effect of TRIM33 on the progress of ccRCC. Method. The Cancer Genome Atlas (TCGA) database was used to examine the mRNA expression levels of TRIM33 in ccRCC tissues and its clinical relevance. Immunohistochemistry (IHC) was performed to evaluate its expression in ccRCC tissues obtained from our hospital. The correlation between TRIM33 expression and clinicopathological features of the patients was also investigated. The effects of TRIM33 on the proliferation of ccRCC cells were examined using the CCK-8 and colony formation assays. The effects of TRIM33 on the migration and invasion of ccRCC cells were explored through wound healing and transwell assays, along with the use of Wnt signaling pathway agonists in rescue experiments. Western blotting was used to explore the potential mechanism of TRIM33 in renal cancer cells. A xenograft model was used to explore the effect of TRIM33 on tumor growth. Result. Bioinformatics analysis showed that TRIM33 mRNA expression in ccRCC tissues was downregulated, and low TRIM33 expression was related to poor prognosis in ccRCC patients. In agreement with this, low TRIM33 expression was detected in human ccRCC tissues. TRIM33 expression levels were correlated with clinical characteristics, including tumor size and Furman’s grade. Furthermore, TRIM33 overexpression inhibited proliferation, migration, and invasion of 786-O and ACHN cell lines. The rescue experiment showed that the originally inhibited migration and invasion capabilities were restored. TRIM33 overexpression reduced the expression levels of β-catenin, cyclin D1, and c-myc, and inhibited tumor growth in ccRCC cells in vivo. Conclusion. TRIM33 exhibits an abnormally low expression in human ccRCC tissues. TRIM33 may serve as a potential therapeutic target and prognostic marker for ccRCC.

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