scholarly journals TPL Inhibits the Invasion and Migration of Drug-Resistant Ovarian Cancer by Targeting the PI3K/AKT/NF-κB-Signaling Pathway to Inhibit the Polarization of M2 TAMs

2021 ◽  
Vol 11 ◽  
Author(s):  
Fuyin Le ◽  
Lilan Yang ◽  
Yiwen Han ◽  
Yanying Zhong ◽  
Fuliang Zhan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
Dependent Manner ◽  
Tumor Associated Macrophages ◽  
Invasion And Migration ◽  
And Migration

Chemoresistance is the primary reason for the poor prognosis of patients with ovarian cancer, and the search for a novel drug treatment or adjuvant chemotherapy drug is an urgent need. The tumor microenvironment plays key role in the incidence and development of tumors. As one of the most important components of the tumor microenvironment, M2 tumor-associated macrophages are closely related to tumor migration, invasion, immunosuppressive phenotype and drug resistance. Many studies have confirmed that triptolide (TPL), one of the principal components of Tripterygium wilfordii, possesses broad-spectrum anti-tumor activity. The aims of this study were to determine whether TPL could inhibit the migration and invasion of A2780/DDP cells in vitro and in vivo by inhibiting the polarization of M2 tumor-associated macrophages (TAMs); to explore the mechanism(s) underlying TPL effects; and to investigate the influence of TPL on murine intestinal symbiotic microbiota. In vitro results showed that M2 macrophage supernatant slightly promoted the proliferation, invasion, and migration of A2780/DDP cells, which was reversed by TPL in a dose-dependent manner. Animal experiments showed that TPL, particularly TPL + cisplatin (DDP), significantly reduced the tumor burden, prolonged the life span of mice by inhibiting M2 macrophage polarization, and downregulated the levels of CD31 and CD206 (CD31 is the vascular marker and CD206 is the macrophage marker), the mechanism of which may be related to the inhibition of the PI3K/Akt/NF-κB signaling pathway. High-throughput sequencing results of the intestinal microbiota in nude mice illustrated that Akkermansia and Clostridium were upregulated by DDP and TPL respective. We also found that Lactobacillus and Akkermansia were downregulated by DDP combined with TPL. Our results highlight the importance of M2 TAMs in Epithelial Ovarian Cancer (EOC) migration ability, invasiveness, and resistance to DDP. We also preliminarily explored the mechanism governing the reversal of the polarization of M2 macrophages by TPL.

scholarly journals LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qi Yang ◽  
Yu-Jie Dong
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Ovarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo. Results Significant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified. Conclusion SNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.

scholarly journals Sulfated Polysaccharide From Undaria Pinnatifida Induces Apoptosis and Inhibits Proliferation, Migration, and Invasion in Ovarian Cancer via Suppressing the Hedgehog Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Yang ◽  
Qin Zhang ◽  
Yongping Xu ◽  
Gang Chen ◽  
Yukuan Qiu
Keyword(s):  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Undaria Pinnatifida ◽  
Sulfated Polysaccharide ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Hh Signaling

Objective: To investigate the effects of sulfured polysaccharide from Undaria pinnatifida (SPUP) on the biological behaviors of ovarian cancer (OC) cells and its potential mechanism.Methods: Sulfated polysaccharide from Undaria pinnatifida (SPUP) was extracted and characterized through a combination of chemical analysis, IR spectra, UV-Vis, gas chromatography, and high-performance gel permeation chromatography. OC and human ovarian surface epithelial cells were used as working model in vitro for evaluation of SPUP’s therapeutic effects. A combination of CCK-8, Transwell, and flow cytometry assay was used to measure the proliferation, migration, invasion, and apoptosis of OC cells, respectively. In addition, the protein expression levels of cells were also measured by Western blot.Results: SPUP suppressed OC development from three different perspectives: 1) SPUP treatment significantly inhibited the proliferation of OC in a dosage-dependent manner (p < 0.05); 2) SPUP inhibited the migration and invasion of OC cells confirmed by scratch and Transwell experiments (p < 0.05); 3) SPUP induced apoptosis in OC cells and thus further inhibited the growth of OC cells evaluated using flow cytometry (p < 0.05). The underlying mechanism of the suppressing effects of SPUP might be related to the inhibition of the hedgehog (Hh) signaling pathway in OC cells after SPUP treatment. With additional suppression of the Hh signaling pathway, the anticancer effects of SPUP were enhanced (p < 0.05).Conclusion: Taken together, SPUP could inhibit the proliferation, migration, and invasion and induce apoptosis of OC cells by inhibiting the activation of the Hh signaling pathway, which proposes SPUP as a novel drug to treat OC clinically.

scholarly journals Osthole Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Cervical Carcinoma HeLa Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Sugai Yin ◽  
Hejuan Liu ◽  
Jing Wang ◽  
Shuying Feng ◽  
Yulong Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Cancer Metastasis ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Human Cervical Carcinoma ◽  
And Migration

Purpose. To study the effect of osthole extract on proliferation, migration, invasion, and apoptosis of human cervical carcinoma HeLa cells and investigate its underlying mechanism. Methods. HeLa cells were exposed to osthole at various concentrations. Cell viability, migration, and invasion were detected by MTT assay, scratch wound-healing assay, and invasion assay, respectively. The proportion of cells undergoing apoptosis was analyzed by flow cytometry. Western blot and RT-qPCR were performed to determine changes in the expression of key factors in the Wnt/β-catenin signaling pathway. Results. The osthole extract effectively inhibited the proliferation, migration, and invasion potential of HeLa cells in a dose-dependent manner. The rate of apoptosis induction in HeLa cells treated with the osthole extract for 48 h was significantly higher than that of the untreated controls. Outcomes of the western blotting analysis and RT-qPCR showed that the expression of β-catenin, c-Myc, cyclin D1, survivin, and MMP-9 was significantly inhibited. Conclusion. Osthole could significantly inhibit the malignant behavior of HeLa cells and induce cellular apoptosis. Inactivation of the Wnt/β-catenin signaling pathway by osthole may be a mechanism to control cancer metastasis.

Mechanism of miR-590-3p carried by tumor-derived extracellular vesicles in promoting invasion and metastasis of ovarian cancer

2021 ◽  
Author(s):  
Yunyun Zheng ◽  
Kang Zhu ◽  
Guihu Wang
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Gynecologic Malignancy ◽  
Promoting Effect ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Ovarian cancer (OC) remains a common gynecologic malignancy. Tumor-derived extracellular vesicles (EVs) contribute to pro-metastasis microenvironment by carrying microRNAs (miRs). This study investigated the mechanism of miR-590-3p carried by OC cell-derived EVs in OC metastasis. Methods miR-590-3p expression in OC tissues and cells was measured. EVs were extracted from healthy serum and the serum of patients with OC or metastatic OC. EVs were extracted from OC cells and normal OC epithelial cells in vitro. miR-590-3p expression in EVs was tested. The effect of EVs-miR-590-3p on the proliferation, migration and invasion of OC cells was measured. The target of miR-590-3p was predicted and verified. The effect of miR-590-3p targeting CPEB3 on OC cells was confirmed by functional rescue assays. Xenograft tumor experiment was performed to verify the mechanism of EVs-miR-590-3p in the tumorigenesis and metastasis of OC. Results miR-590-3p expression was enhanced in OC, and correlated with OC metastasis. miR-590-3p was elevated in OC cell-derived EVs and could be transferred to other OC cells by EVs. OC cell-derived EVs facilitated proliferation, invasion and migration of OC cells by transferring miR-590-3p. miR-590-3p targeted CPEB3. Overexpressing CPEB3 repressed the promoting effect of EVs-miR-590-3p on OC cells. In vivo experiment confirmed that EVs-miR-590-3p facilitated tumorigenesis and metastasis of OC cells by targeting CPEB3. Conclusion OC cell-derived EVs facilitated progression and metastasis of OC via the miR-590-3p/CPEB3 axis.

scholarly journals Erratum

2021 ◽  
Vol 28 (6) ◽  
pp. 681-682
Author(s):  
Juan Gu ◽  
Chang-fu Cui ◽  
Li Yang ◽  
Ling Wang ◽  
Xue-hua Jiang
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Mrna Level ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Downstream Target ◽  
And Migration

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and -catenin. Emodin also significantly inhibited the activation of the Wnt/-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/-catenin signaling pathway.

scholarly journals Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qingjuan Meng ◽  
Ningning Wang ◽  
Guanglan Duan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Invasion And Migration ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

scholarly journals Metformin Inhibited Growth, Invasion and Metastasis of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

2018 ◽  
Vol 51 (3) ◽  
pp. 1276-1286 ◽  
Author(s):  
Feng Liang ◽  
Yu-Gang Wang ◽  
Changcheng Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Plasma Glucose Level ◽  
Caspase 3 ◽  
Time Dependent ◽  
Dependent Manner ◽  
Metformin Treatment ◽  
Invasion And Migration ◽  
And Migration

Background/Aims: This study aimed at investigating the effects of metformin on the growth and metastasis of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Methods: Two human ESCC cell lines EC9706 and Eca109 were selected and challenged with metformin in this study. Western blot assay was performed to detect th level of Bcl-2, Bax and Caspase-3. Scratch wound assay, transwell assay and Millicell invasion assay were used to assay the invasion and migration of EC9706 and Eca109 cells. Nude mice tumor models were used to assay the growth and lung metastasis of ESCC cells after metformin treatment. The plasma glucose level was also assayed. Results: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated. Metformin significantly inhibited the invasion and migration of EC9706 and Eca109 cells (p < 0.05). mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p < 0.05). In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9. Moreover, we showed that metformin treatment did not cause significant alteration in liver and renal functions and plasma glucose level. Conclusion: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9. As a whole, our results indicate the potential of metformin to be developed as a chemotherapeutic agent for patients with ESCC and might stimulate future studies on this area.

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