Cancer Biomarkers
·
2019
·Vol. 24
·期 4
·469-475
·
IF 2.859
Qin Yujing,Li Wenxue,Long Yingli,Zhan Zhijia
OBJECTIVE: This study aims to determine the correlation between p-cofilin expression and cisplatin resistance in patients with ovarian cancer, and also to investigate the role of p-cofilin in prognosis. PATIENTS AND METHODS: The ovarian cancer cell line A2780/DDP resistant to cisplatin was prepared. The cell resistance to cisplatin was measured via MTT assay. The cell invasion capacity was identified via Transwell assay. The mRNA expression and protein level was evaluated via semi-quantitative PCR and Western blot, respectively. The tumor tissues of patients with cisplatin-resistant ovarian cancer were collected. The relationship between prognosis and p-cofilin expression was analyzed. RESULTS: The growth rate of A2780 was similar to that of A2780/DDP. The sensitivity of A2780 to cisplatin was significantly higher than that of A2780/DDP (p< 0.01). The migration capacity of A2780/DDP was significantly increased compared to that of A2780 (p< 0.01), indicating that the cisplatin-resistant cell lines were successfully constructed. Both CFL1 mRNA level and p-cofilin level in A2780/DDP was significantly higher than that in A2780 (p< 0.01). The p-cofilin level in cancer tissues in patients with cisplatin-resistant ovarian cancer was significantly higher than that in patients with cisplatin-sensitive ovarian cancer (p< 0.01). The cisplatin resistance was positively correlated with the p-cofilin expression level (r= 0.802, p= 0.023). The survival time of patients with normal or low level of p-cofilin was significantly longer than that of patients with high expression. CONCLUSION: The cisplatin resistance of ovarian cancer is closely related to the expression level of p-cofilin, which affects the prognosis of patients with ovarian cancer.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2023
·Vol. 6
·期 1
·1-14
·
IF 5.9
Zhu Haixia,Wen Zongzhuang,Zhang Aizhen,Liu Dongyue,Wang Hongxiang,Cheng Yin,Yang Xing,Xiao Yu,Li Jianyuan,Sun Daqing,Wu Bin,Gao Jiangang
Spermatogenesis is an extremely complex process, and any obstruction can cause male infertility. RhoGDIα has been identified as a risk of male sterility. In this study, we generate RhoGDIα knockout mice, and find that the males have severely low fertility. The testes from RhoGDIα −/− mice are smaller than that in WT mice. The numbers of spermatogonia and spermatocytes are decreased in RhoGDIα −/− testis. Spermatogenesis is compromised, and spermatocyte meiosis is arrested at zygotene stage in RhoGDIα −/− mice. Acrosome dysplasia is also observed in sperms of the mutant mice. At the molecular level, RhoGDIα deficiency activate the LIMK/cofilin signaling pathway, inhibiting F-actin depolymerization, impairing testis and inducing low fertility in mouse. In addition, the treatment of RhoGDIα −/− mice with Rac1 inhibitor NSC23766 alleviate testis injury and improve sperm quality by inhibiting the LIMK/cofilin/F-actin pathway during spermatogenesis. Together, these findings reveal a previously unrecognized RhoGDIα/Rac1/F-actin-dependent mechanism involved in spermatogenesis and male fertility.
研究领域:
生殖生物学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2025
·Vol. 39
·期 9
·e70453
·
IF 2.8
Dongfang Hu,Zihui Shen,Xueke Hou,Zhishuai Wan,Xiaoyu Guo,Lingli Chen,Zhihong Yin,Hongmei Ning,Yaming Ge
Florfenicol (FLO), a widely used antibiotic, can cause early embryonic death and impaired angiogenesis. However, the mechanism by which FLO inhibits angiogenesis and its role in FLO-induced embryonic toxicity are not yet fully understood. This study aimed to investigate the effect of FLO on the proliferation and migration of mouse bEnd.3 endothelial cells (bECs) and the underlying mechanism, given the crucial role of endothelial cells in angiogenesis. The results showed that FLO treatment at 7.5–15 μg/mL significantly inhibited proliferation and migration in a time-dependent manner, with stronger effects observed after 48 h compared to 24 h. RNA sequencing analysis identified 1351 genes differentially expressed in response to FLO. Functional analysis indicated that FLO disrupted ATP metabolism, angiogenesis, vasculature development, and actin filament organization. The F-actin cytoskeleton remodeling was morphologically confirmed, and activation of the ROCK/Cofilin signaling pathway was detected. Subsequent experiments demonstrated that pharmacological inhibition of the pathway normalized cytoskeletal rearrangement and promoted angiogenesis, as evidenced by enhanced wound closure and increased cell viability. Our results demonstrated that ROCK-mediated F-actin remodeling plays a crucial role in the FLO-induced inhibition of proliferation and migration in bECs. These findings may explain why FLO inhibited angiogenesis. However, further investigations are necessary to validate our findings in in vivo experiments.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
毒理学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Lei Lin,Liming Xu,Weijie Sun,Lili Liang,Xiaoliang Qi,Yun-e Zhao
Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.
研究领域:
眼科学
·
细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2016
·Vol. 39
·期 4
·1391-1403
·
IF 4.652
Zhang Lei,Jiang Guoliang,Zhao Xueling,Gong Yuekun
Background/Aims: We investigated the role of dimethyloxalylglycine (DMOG) in bone marrow mesenchymal stem cell (BMSC) osteogenesis mediated by RhoA/ROCK. Methods: BMSCs were cultured with and without DMOG and/or Y-27632 (ROCK1 inhibitor). Cell proliferation, alkaline phosphatase (ALP) levels, and calcium deposits were determined. The expression of Runx2, OSX, p-cofilin, RhoA, and GTP-bound RhoA was determined by real-time RT-PCR and Western blot. Rho-associated coiled-coil-containing protein kinase (ROCK) activity was determined by measuring the phosphorylation of myosin-binding subunit of myosin phosphatase using an ELISA kit. Actin morphology was observed by immunofluorescence. Results: After 24 h, DMOG (0.5 mM) increased the expression of GTP-bound RhoA (+141%, P < 0.001) and enhanced ROCK activity (315%, P < 0.001). DMOG (0.5 mM) enhanced ALP levels after 3, 7, and 21 days of osteogenic induction (all P < 0.001) and strengthened calcium deposition (P < 0.001). In addition, compared with controls, DMOG (0.5 mM) increased the mRNA levels of osteogenesis genes RUNX2 and OSX (all P < 0.001). Furthermore, compared with controls, DMOG increased the expression of p-cofilin (+57%, P < 0.001), which resulted in rearrangement of actin filaments. All these effects were abolished, at least in part, by Y-27632. Conclusion: DMOG promotes BMSC osteogenic differentiation via activation of RhoA/ROCK, suggesting clues for future therapies using BMSCs
研究领域:
干细胞生物学
·
骨骼生物学
·
细胞信号传导
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Xianglong Tang,Zhen Wang,Yandong Xie,Yuyang Liu,Kun Yang,Taiping Li,Hong Shen,Mengjie Zhao,Juan Jin,Hong Xiao,Hongyi Liu,Ning Gu
Radiotherapy-resistant glioblastoma (rrGBM) remains a significant clinical challenge because of high infiltrative growth characterized by activation of antiapoptotic signal transduction. Herein, we describe an efficiently biodegradable selenium-engineered mesoporous silica nanocapsule, initiated by high-energy X-ray irradiation and employed for at-site RNA interference (RNAi) to inhibit rrGBM invasion and achieve maximum therapeutic benefit. Our radiation-triggered RNAi nanocapsule showed high physiological stability, good blood-brain barrier transcytosis, and potent rrGBM accumulation. An intratumoral RNAi nanocapsule permitted low-dose X-ray radiation-triggered dissociation for cofilin-1 knockdown, inhibiting rrGBM infiltration. More importantly, tumor suppression was further amplified by electron-affinity aminoimidazole products converted from metronidazole polymers under X-ray radiation-exacerbated hypoxia, which sensitized cell apoptosis to ionizing radiation by fixing reactive oxygen species-induced DNA lesions. In vivo experiments confirmed that our RNAi nanocapsule reduced tumor growth and invasion, prolonging survival in an orthotopic rrGBM model. Generally, we present a promising radiosensitizer that would effectively improve rrGBM-patient outcomes with low-dose X-ray irradiation.
研究领域:
纳米技术
·
癌症生物学
·
放射生物学
·
药学
·
神经肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）