scholarly journals Salinomycin Exerts Anticancer Effects on PC-3 Cells and PC-3-Derived Cancer Stem Cells In Vitro and In Vivo

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yunsheng Zhang ◽  
Luogen Liu ◽  
Fang Li ◽  
Tao Wu ◽  
Hongtao Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Xenograft Model ◽  
Mechanistic Study ◽  
Prostate Cell ◽  
Downstream Target ◽  
Prostate Cancer Stem Cells

Salinomycin is an antibiotic isolated from Streptomyces albus that selectively kills cancer stem cells (CSCs). However, the antitumor mechanism of salinomycin is unclear. This study investigated the chemotherapeutic efficacy of salinomycin in human prostate cancer PC-3 cells. We found that cytotoxicity of salinomycin to PC-3 cells was stronger than to nonmalignant prostate cell RWPE-1, and exposure to salinomycin induced G2/M phage arrest and apoptosis of PC-3 cells. A mechanistic study found salinomycin suppressed Wnt/β-catenin pathway to induce apoptosis of PC-3 cells. An in vivo experiment confirmed that salinomycin suppressed tumorigenesis in a NOD/SCID mice xenograft model generated from implanted PC-3 cells by inhibiting the Wnt/β-catenin pathway, since the total β-catenin protein level was reduced and the downstream target c-Myc level was significantly downregulated. We also showed that salinomycin, but not paclitaxel, triggered more apoptosis in aldehyde dehydrogenase- (ALDH-) positive PC-3 cells, which were considered as the prostate cancer stem cells, suggesting that salinomycin may be a promising chemotherapeutic to target CSCs. In conclusion, this study suggests that salinomycin reduces resistance and relapse of prostate tumor by killing cancer cells as well as CSCs.

scholarly journals High expression of PSMC2 promotes gallbladder cancer through regulation of GNG4 and predicts poor prognosis

Oncogenesis ◽  
2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Dawei Zhu ◽  
Xing Gu ◽  
Zhengyu Lin ◽  
Dandan Yu ◽  
Jing Wang
Keyword(s):  
Gallbladder Cancer ◽  
Malignant Tumor ◽  
Xenograft Model ◽  
Tumor Grade ◽  
Significant Inhibition ◽  
Mechanistic Study ◽  
Downstream Target ◽  
Advanced Tumor

AbstractGallbladder cancer (GBC) is a common malignant tumor of the biliary tract, which accounts for 80–95% of biliary tumors worldwide, and is the leading cause of biliary malignant tumor-related death. This study identified PSMC2 as a potential regulator in the development of GBC. We showed that PSMC2 expression in GBC tissues is significantly higher than that in normal tissues, while high PSMC2 expression was correlated with more advanced tumor grade and poorer prognosis. The knockdown of PSMC2 in GBC cells induced significant inhibition of cell proliferation, colony formation and cell motility, while the promotion of cell apoptosis. The construction and observation of the mice xenograft model also confirmed the inhibitory effects of PSMC2 knockdown on GBC development. Moreover, our mechanistic study recognized GNG4 as a potential downstream target of PSMC2, knockdown of which could aggravate the tumor suppression induced by PSMC2 knockdown in vitro and in vivo. In conclusion, for the first time, PSMC2 was revealed as a tumor promotor in the development of GBC, which could regulate cell phenotypes of GBC cells through the interaction with GNG4, and maybe a promising therapeutic target in GBC treatment.

scholarly journals Chemosensitization of prostate cancer stem cells in mice by angiogenin and plexin-B2 inhibitors

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Shuping Li ◽  
Kevin A. Goncalves ◽  
Baiqing Lyu ◽  
Liang Yuan ◽  
Guo-fu Hu
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ribosomal Rna ◽  
Protein Translation ◽  
Chemotherapeutic Agents ◽  
Self Renewal ◽  
5S Ribosomal Rna ◽  
Prostate Cancer Stem Cells

AbstractCancer stem cells (CSCs) are an obstacle in cancer therapy and are a major cause of drug resistance, cancer recurrence, and metastasis. Available treatments, targeting proliferating cancer cells, are not effective in eliminating quiescent CSCs. Identification of CSC regulators will help design therapeutic strategies to sensitize drug-resistant CSCs for chemo-eradication. Here, we show that angiogenin and plexin-B2 regulate the stemness of prostate CSCs, and that inhibitors of angiogenin/plexin-B2 sensitize prostate CSCs to chemotherapy. Prostate CSCs capable of self-renewal, differentiation, and tumor initiation with a single cell inoculation were identified and shown to be regulated by angiogenin/plexin-B2 that promotes quiescence and self-renewal through 5S ribosomal RNA processing and generation of the bioactive 3′-end fragments of 5S ribosomal RNA, which suppress protein translation and restrict cell cycling. Monoclonal antibodies of angiogenin and plexin-B2 decrease the stemness of prostate CSCs and sensitize them to chemotherapeutic agents in vitro and in vivo.

scholarly journals Replication Study: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Xuefei Yan ◽  
Beibei Tang ◽  
Biao Chen ◽  
Yongli Shan ◽  
Huajun Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Binding Sites ◽  
Cancer Biology ◽  
Original Study ◽  
Cd44 Expression ◽  
Prostate Cancer Stem Cells ◽  
Significant Difference

As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.

α2β 1HI/CD133+ PROSTATE CANCER STEM CELLS FROM HUMAN TUMOURS ARE HIGHLY TUMORIGENIC IN VIVO

2006 ◽  
Vol 5 (14) ◽  
pp. 790 ◽  
Author(s):  
A. Collins ◽  
K. Hyde ◽  
P. Berry ◽  
K. Linton ◽  
F. Hamdy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Human Tumours ◽  
Prostate Cancer Stem Cells

scholarly journals 698. Eliminating TLR9+ Prostate Cancer Stem Cells In Vivo Using NF-kB/RELA- or STAT3-Targeting CpG-siRNA Conjugates

2015 ◽  
Vol 23 ◽  
pp. S278
Author(s):  
Dayson F. Moreira ◽  
Qifang Zhang ◽  
Dewan M. Hossain ◽  
Sergey Nechaev ◽  
Haiqing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Prostate Cancer Stem Cells

scholarly journals MiR-197 Inhibitor Loaded AbCD133@MSNs@GNR Affects the Development of Prostate Cancer Through Targeting ITGAV

2021 ◽  
Vol 9 ◽  
Author(s):  
Guanqun Ju ◽  
Yingjian Zhu ◽  
Tao Du ◽  
Wanli Cao ◽  
Jianhai Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Drug Carrier ◽  
Integrin Subunit ◽  
Prostate Cancer Cells ◽  
Prostate Cancer Stem Cells

Prostate cancer is one of the most severe male malignant tumors, which ranks second in mortality rate among all tumors. Traditional methods of treatment for prostate cancer produce obvious side effects and a high recurrence rate. Cancer stem cells are considered to be a group of cells that determine the proliferation, metastasis, and drug resistance of tumor. Prostate cancer therapy based on microRNAs and prostate cancer stem cells (PCSCs) has been a research hot spot in this field. Previous studies have reported that miR-197 plays an important role in the occurrence and development of prostate cancer, but the molecular mechanism of miR-197 on the development of prostate cancer has not been reported yet. In this study, we verified that miR-197 is significantly overexpressed in prostate cancer tissues and prostate cancer cells. Then, we verified that miR-197 expression affects the proliferation, invasion, and metastasis of prostate cancer cells by regulating integrin subunit alpha V (ITGAV) expression through STAT5 pathway, and the results indicated that the miR-197 inhibitor can be a prostate cancer suppressor. Then we synthesized the AbCD133@GNR@MSNs@miR-197 inhibitor drug carrier, in which 35.42 μg of the miR-197 inhibitor could be loaded in 1 mg of AbCD133@GNR@MSNs. The AbCD133@GNR@MSNs@miR-197 inhibitor demonstrated good photothermal properties and photothermal controlled-release properties. The modified CD133 antibodies on the surface of the nano drug carrier helped more drug carriers to enter the PCSCs. The pharmacodynamic effects of the AbCD133@GNR@MSNs@miR-197 inhibitor on PCSCs in vivo and in vitro were studied under near-infrared radiation. The results showed that the AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could not only significantly suppress the development of PCSCs through ITGAV/STAT5 pathway but also significantly suppress the growth of PCSC solid tumors. In short, our study verified that miR-197 regulates the development of PCSCs through STAT5 pathway by targeting ITGAV, and the AbCD133@MSNs@GNR@miR-197 inhibitor could be a potential suppressor used in prostate cancer treatment. In short, our study found that miR-197 affected the development of prostate cancer by regulating ITGAV. The AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could suppress the development and growth of PCSCs in vitro and in solid tumors not only by targeting the ITGAV but also through photothermal therapy. Our study not only provides a theoretical basis for the clinical treatment of prostate cancer but also provides a research scheme of drug loading and microRNA-based photothermal controlled therapy for prostate cancer.

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