Cell adhesion and invasion inhibitory effect of an ovarian cancer targeting peptide selected via phage display in vivo

2014 ◽  
Vol 443 (3) ◽  
pp. 858-863 ◽  
Author(s):  
Ximing Pu ◽  
Chuying Ma ◽  
Guangfu Yin ◽  
Fei You ◽  
Yan Wei
Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770550 ◽  
Author(s):  
Yi Li ◽  
Ming Xiao ◽  
Fangchun Guo

SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.


Author(s):  
Yanli Wang ◽  
Jia Li ◽  
Chunling Xu ◽  
Xiaomeng Zhang

Increasing evidence indicates that the dysregulation of microRNAs is associated with the development and progression of various cancers. MicroRNA-139-5p (miR-139-5p) has been reported to have a tumor suppressive role in many types of cancers. The role of miR-139-5p in ovarian cancer (OC) is poorly understood. The purpose of the present study was to explore the expression of miR-139-5p and its function in OC. The results showed that miR-139-5p expression was markedly downregulated in OC tissues and cell lines. In addition, underexpression of miR-139-5p was significantly associated with FIGO stage, lymph mode metastasis, and poor overall survival of OC patients. Functional analyses indicated that overexpression of miR-139-5p significantly inhibited proliferation, colony formation, migration, and invasion of OC cells. Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) was identified as a direct target of miR-139-5p using luciferase reporter assays, qualitative real-time reverse transcriptase PCR (qRT-PCR), and Western blot. In addition, ROCK2 expression was upregulated and was inversely correlated with miR-139-5p levels in OC tissues. Rescue experiments showed that overexpression of ROCK2 effectively reversed the inhibitory effect of OC cells induced by miR-139-5p. Most interestingly, in vivo studies indicated that miR-139-5p markedly suppressed the growth of tumors by repressing ROCK2 expression in nude mice. Taken together, these findings demonstrated that miR-139-5p plays an important tumor suppressor role in OC by directly binding to ROCK2, providing a novel target for the molecular treatment of OC.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun Leng ◽  
Can Zhao ◽  
Guoliang Yan ◽  
Shuangyue Xu ◽  
Yinggui Yang ◽  
...  

Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.


2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Mallika Asar ◽  
Jessica Newton‐Northup ◽  
Susan Deutscher ◽  
Mette Soendergaard

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Lindsey Weintraub ◽  
James Rudy ◽  
Susan Hum‐Musser ◽  
Richard Musser ◽  
Mette Soendergaard

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Yangqiu Jin ◽  
Hui Wang

Abstract Background Circular RNA (circRNA) has been shown to be involved in the regulation of human disease progression, including ovarian cancer (OC). Circ_0078607 was found to participate in OC progression. But its function and mechanism in OC deserve further exploration. Methods The expression levels of circ_0078607, salt-inducible kinase 1 (SIK1) and microRNA (miR)-32-5p were examined by qRT-PCR. And the protein expression levels of SIK1, metastasis marker and apoptosis marker were determined using western blot analysis. EDU staining, colony formation assay, transwell assay and flow cytometry were used to detect the proliferation, migration, invasion and apoptosis of cells. Moreover, dual-luciferase reporter assay was employed to verify the interaction between miR-32-5p and circ_0078607 or SIK1. Xenograft models were constructed to perform in vivo experiments. Results Circ_0078607 and SIK1 were downregulated in OC tissues and cells. Overexpressed circ_0078607 and SIK1 could inhibit OC cell proliferation, migration, invasion, and promote apoptosis. MiR-32-5p could be sponged by circ_0078607, and its overexpression could reverse the suppressive effect of circ_0078607 on OC progression. Furthermore, SIK1 was a target of miR-32-5p, and circ_0078607 could regulate SIK1 by sponging miR-32-5p. The inhibitory effect of circ_0078607 on OC progression also could be reversed by SIK1 silencing. In vivo experiments showed that circ_0078607 reduced OC tumorigenesis by regulating the miR-32-5p/SIK1 axis. Conclusion Circ_0078607 could serve as a sponge of miR-32-5p to regulate SIK1 expression, thereby inhibiting OC progression.


2021 ◽  
Author(s):  
Xiaodi Li ◽  
Yanwen Fang ◽  
Zhicai Fang ◽  
Ping Wang ◽  
Jun Zhu

Abstract To estimate the effect of a steady-state magnetic field (SMF) with low magnetic intensity gradient on the apoptosis-promoting factors related to cancer cells, we systematically select SMF with 0.2T, 0.4T and 0.6T to study their effect on different ovarian cancer lines. An in vitro cell model system about two kinds of ovarian cancer lines is established, whose viability and intracellular factors are detected by CCK-8, confocal microscopy and flow cytometry method. The results demonstrate that the apoptosis rate of ovarian cancer cells is increased with the enhancement of SMF magnetic intensity. Furthermore, we detect an increasing ROS and intracellular Ca2+ levels in ovarian cancer cells, which can be caused by SMF. The results suggest that ROS and Ca2+ levels are the main reason for the significant apoptosis of ovarian cancer cell lines in SMF. Moreover, an in vivo experiment also reveals that SMF has a strong inhibitory effect on ovarian cancer. Therefore, the inhibitory strategy is an effective, which has a great potential in the treatment of drug-resistant ovarian cancer.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1141
Author(s):  
Kae Nakamura ◽  
Nobuhisa Yoshikawa ◽  
Yuko Mizuno ◽  
Miwa Ito ◽  
Hiromasa Tanaka ◽  
...  

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The major cause of EOC’s lethality is that intraperitoneal recurrence occurs with high frequency due to occult metastasis. We had demonstrated that plasma-activated medium (PAM) exerts a metastasis-inhibitory effect on ovarian cancer in vitro and in vivo. Here we investigated how PAM inhibits intraperitoneal metastasis. We studied PAM’s inhibition of micro-dissemination onto the omentum by performing in vivo imaging in combination with a sequential histological analysis. The results revealed that PAM induced macrophage infiltration into the disseminated lesion. The iNOS-positive signal was co-localized at the macrophages in the existing lesion, indicating that PAM might induce M1-type macrophages. This may be another mechanism of the antitumor effect through a PAM-evoked immune response. Intraperitoneal lavage with plasma-activated lactate Ringer’s solution (PAL) significantly improved the overall survival rate in an ovarian cancer mouse model. Our results demonstrated the efficiency and practicality of aqueous plasma for clinical applications.


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