Oncology Letters
·
2017
·Vol. 14
·期 5
·5307-5312
·
IF 1.39
Binggao Wang,Zhibo Xing,Fengmei Wang,Xinyan Yuan,Yanhui Zhang
In order to improve outcomes after breast cancer treatment, it is essential to understand the mechanisms of action of potential therapeutic agents. The effect of fangchinoline (FAN) on migration and apoptosis of human breast cancer MDA-MB-231 cells and its underlying mechanisms were investigated. MDA-MB-231 cells were treated with different concentrations of FAN, growth inhibition rates were measured by MTT assay and morphological changes of apoptotic cells were observed by Hoechst staining. The wound-healing assay was used to determine of the effect of FAN on the migration of MDA-MB-231 cells. ELISA was used to detect the expression of MMP-2 and -9 in MDA-MB-231 cells treated with different concentrations of FAN and western blot analysis was used to quantify expression of NF-κβ and Iκβ proteins in the same cells. Our results showed that FAN significantly inhibited the growth of MDA-MB-231 cells in concentration-dependent manner and it induced MDA-MB‑231 cell apoptosis. With the high FAN concentrations and long exposure times, the levels of MMP-2 and -9 decreased and the expression of NF-κβ decreased, while the expression of Iκβ protein increased. Based on these results, the antitumor effects of FAN on breast cancer cells can be explained at least partially by inducing apoptosis and inhibiting the migration of MDA-MB-231 cells.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 54
·31264-31273
·
IF 3.049
Wei Li,Cheng Tao,Jiexin Wang,Yuan Le,Jianjun Zhang
The complex construction within the oral cavity causes incomplete surgical resection of oral squamous cell carcinoma (OSCC) that may enhance the risk of recurrence and metastasis in the treatment. In situ forming injectable hydrogels with minimally invasive procedures, encapsulation stability and stimuli-responsive degradation have emerged as promising carriers for local drug delivery. In this study, doxorubicin (DOX) was first encapsulated in biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA) micelles and then loaded into an in situ injectable hyaluronic acid (HA) hydrogel, which was cross-linked by a matrix metalloproteinase-2 (MMP-2)-responsive peptide (GCRDGPQGIWGQDRCG) through a Michael addition reaction. In vitro studies demonstrated that the HA hydrogel had a sensitive MMP-2-responsive drug release profile. Investigations including MTT, live-dead, apoptosis, and wound healing assays illustrated that DOX micelle-loaded HA hydrogels exhibited outstanding cytotoxicity against squamous carcinoma cells (SCC-15). Furthermore, by in vivo studies, we also proved that HA hydrogels degraded faster in the tumor site than in normal tissue, which led to a local sustained release of DOX-loaded micelles and tumor growth inhibition of oral squamous cell carcinoma (OSCC) without any damage to the organs. Therefore, this work provides a remarkable drug delivery platform for local chemotherapy and other applications.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
Genes & Genomics
·
2022
·Vol. 44
·期 11
·1375-1384
·
IF 2.164
Wang Yazhuo,Ren Yanan,Li Na,Zhao Jing,Zhao Sufen
Background Rab11a is a novel identified tumorigenic factor involved in different cancers. Objective This study aimed to assess the biological function of Rab11a in ovarian cancer (OC). Methods GEPIA database and real-time PCR were used to determine Rab11a expression in OC tissues and normal ovarian tissues. CCK-8, cell cycle, wound healing, transwell, and enzyme linked immunosorbent assay were used to detect the effects of Rab11a knockdown or overexpression on the proliferation, migration, and invasion of OC cells. Western blot analysis of autophagy-related markers and immunofluorescence staining of LC3 were performed to determine autophagy induction in Rab11a-silenced or overexpressed OC cells. Moreover, autophagy inhibitor 3-MA was employed to clarify the effects of Rab11a-regulated autophagy on the malignant phenotypes of OC cells. Results The mRNA level of Rab11a was increased in tumor tissues from OC patients as compared to the normal ovarian tissues. Knockdown of Rab11a in OVCAR-3 cells inhibited the growth of OC cells and led to cell cycle arrest, accompanied by reduced expression of PCNA and Cyclin D1. Rab11a deficiency suppressed migration and invasion of OC cells, accompanied by decreased secretion of MMP-2 and MMP-9. Silence of Rab11a impeded autophagy induction, as evidenced by decreased LC3 puncta formation, reduced abundance of LC3II and Beclin1, and increased p62 protein expression. In contrast, the ectopic expression of Rab11a in A2780 cells exerted opposite effects. Interestingly, autophagy inhibitor 3-MA abolished the effects of Rab11a overexpression on autophagy, proliferation, migration, and invasion. Conclusions Rab11a promotes the malignant phenotypes of OC cells by inducing autophagy.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2024
·
IF 1.6
Dapeng Sun,Chenglong Ye,Zhuo Chen
Matrix metalloproteinase-2 (MMP-2) is a key biomarker involved in various pathological processes, so its sensitive and selective detection is of great clinical significance. A fluorescent sensor for the detection of MMP-2 was successfully designed based on the inner filter effect (IFE) between carbon dots (CDs) and gold nanoparticles (AuNPs). In the presence of MMP-2, peptide chains are hydrolyzed, releasing short peptides that contain thiol groups and positive charges, thereby inducing the aggregation of AuNPs. This aggregation disrupts the IFE between AuNPs and CDs, leading to a significant enhancement of the fluorescence. By monitoring the change in fluorescence intensity of CDs, the concentration of MMP-2 was accurately determined. The sensor exhibited a linear response across the concentration range from 1.0 to 150 ng/mL, with a detection limit as low as 0.23 ng/mL, which is lower than those of previously reported methods. Furthermore, the sensor demonstrated minimal interference from coexisting biochemical substances for MMP-2 in human serum. Notably, the sensor was successfully applied to determine MMP-2 in human serum, showing satisfactory recovery rates ranging from 98.8 to 1106.0%. In conclusion, this fluorescent sensor offers high selectivity and sensitivity for MMP-2 detection, making it a promising tool for clinical diagnosis of related diseases.
研究领域:
生物医学
·
纳米技术
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Xiaoping Wu,Qiujie Pang,Fuxiang Zhi,Xiaohong Mao,Yingbin Hu
The role of long non-coding RNA ACTA2 antisense RNA 1 (LncRNA ACTA2-AS1) in colorectal cancer (CRC) was awaited to be elucidated. Clinical specimen and data on ACTA2-AS1 expression in colon adenocarcinoma (COAD) were collected, followed by in situ hybridization . Transfected CRC cell viability, proliferation, migration, and invasion were determined with Cell Counting Kit-8, colony formation, Scratch, and Transwell assays, respectively. Relative expressions of ACTA2-AS1, PCNA, Bcl-2, MMP-2 and MMP-9 were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot . ACTA2-AS1 expression was downregulated in CRC. Overexpressed ACTA2-AS1 repressed the cell viability, proliferation, migration and invasion, increased cleaved caspase-3 level yet decreased PCNA, Bcl-2, MMP-2 and MMP-9 levels. ACTA2-AS1 silencing, however, did oppositely. Collectively, ACTA2-AS1 inhibits the viability, proliferation, migration and invasion of CRC cells to effectively suppress the progression of CRC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 11
·1516-1521
·
IF 2.378
Fujuan Luan,Zuhong Yu,Ling Yin,Xia Leng,Yuxue Shi,Jie Wang,Haibin Shi,Weichang Chen
Matrix metalloproteinase-2 (MMP-2) plays an important role in tumorigenesis and metastasis of gastric cancer. Therefore, specific and sensitive detection of MMP-2 is of great significance for clinical diagnosis and therapeutic evaluation of gastric cancer. Herein, we developed a new approach for accurate detection of MMP-2 activity both in gastric cancer cells and clinical tissues using a fluorescent probe Dab-PLGVRGY-FITC. The capability of the probe for detecting MMP-2 was systematically evaluated in gastric cancer MGC-803 cells and clinical gastric cancer tissues. Around 40-fold fluorescence enhancement at a wavelength of 520 nm was determined for the assays of the probe with recombinant MMP-2. The detection limit of MMP-2 was as low as 42 ng mL−1. Strong fluorescence signals were detected in MGC-803 cells and mouse gastric cancer tissues. Fluorescence signal enhancements of 11 clinical gastric cancer tissue lysates were 5.8 ∼ 9 times (7.53 ± 0.77 on average) higher than those from gastritis patients. This probe could be potentially used for early diagnosis of gastric cancer in clinics.
研究领域:
肿瘤学
·
生物医学工程
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 11
·1932-1940
·
IF 4.872
Jing-Jing Hu,Li-Han Liu,Ze-Yong Li,Ren-Xi Zhuo,Xian-Zheng Zhang
In this paper, we report on an intelligent mesoporous silica-based multifunctional theranostic nanoplatform (designated as MMTNP) for tumor imaging as well as controlled drug release. This theranostic nanoplatform consists of MCM-41 typical mesoporous silica nanoparticles (MSNs) as a hydrophobic drug carrier, matrix metalloprotease-2 (MMP-2) activated fluorescence imaging peptides on the surface of MSNs served as diagnostic probes as well as enzyme-responsive nanovalves blocking the pores, and cRGD peptides further functionalized on the surface of MSNs for tumor targeting. In the absence of MMP-2 conditions, the proximity between the fluorescent dye 5(6)-carboxytetramethylrhodamine hydrochloride (TAMRA) and the quencher 4,4-dimethylamino-azobenzene-4′-carboxylic acid (Dabcyl) on the surface of MSNs resulted in no fluorescence. When the drug loaded nanoplatform arrived at tumor tissue with overexpressed MMP-2, the fluorescence of TAMRA became recovered efficiently due to the hydrolysis of the MMP-2 sensitive peptide substrate, realizing tumor imaging and triggering drug release. In addition, the further introduced cRGD peptide significantly enhanced the targeting efficiency through receptor-mediated endocytosis in tumor cells.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Liu Ying,Tang Rui,Cao Yuting,Wu Nianhong,Qin Qiaoxi,Chen Yuanyuan,Wei Xi,Ren Jianli,Sun Yang,Zhou Hong,Zhou Yang,Li Pan
Background Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment. Results Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis. Conclusions Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings. Graphical Abstract
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-14
·
IF 10.435
Yang Yuming,Han Yu,Sun Qiuyang,Cheng Jin,Yue Caixia,Liu Yanlei,Song Jie,Jin Weilin,Ding Xianting,de la Fuente Jesús M.,Ni Jian,Wang Xiaoqiang,Cui Daxiang
Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.Conclusion sThe development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
研究领域:
纳米技术
·
肿瘤学
·
药学
·
分子医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2017
·
IF 13.942
Tianjiao Ji,Jiayan Lang,Jing Wang,Rong Cai,Yinlong Zhang,Feifei Qi,Lijing Zhang,Xiao Zhao,Wenjing Wu,Jihui Hao,Zhihai Qin,Ying Zhao,Guangjun Nie
During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via coassembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids. By utilizing the MMP-2-rich pathological environment, the pirfenidone (PFD) loaded MRPL (MRPL-PFD) can specifically release PFD at the pancreatic tumor site and down-regulate the multiple components of ECM expressed by the PSCs. This resulted in a significant increase in the penetration of gemcitabine into the tumor tissue and enhanced the efficacy of gemcitabine for pancreatic tumor. Our design tailored for antifibrosis of pancreatic cancer may provide a practical approach to build functional liposomes through supramolecular assembly, and regulation of ECM may be a promising adjuvant therapeutic strategy for pancreatic and other ECM-rich tumors.
研究领域:
药学
·
肿瘤学
·
生物材料
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 18
·
IF 13.117
Chen-Cheng Xue,Meng-Huan Li,Yang Zhao,Jun Zhou,Yan Hu,Kai-Yong Cai,Yanli Zhao,Shu-Hong Yu,Zhong Luo
The rapid development of treatment resistance in tumors poses a technological bottleneck in clinical oncology. Ferroptosis is a form of regulated cell death with clinical translational potential, but the efficacy of ferroptosis-inducing agents is susceptible to many endogenous factors when administered alone, for which some cooperating mechanisms are urgently required. Here, we report an amorphous calcium carbonate (ACC)–based nanoassembly for tumor-targeted ferroptosis therapy, in which the totally degradable ACC substrate could synergize with the therapeutic interaction between doxorubicin (DOX) and Fe2+. The nanoplatform was simultaneously modified by dendrimers with metalloproteinase-2 (MMP-2)–sheddable PEG or targeting ligands, which offers the functional balance between circulation longevity and tumor-specific uptake. The therapeutic cargo could be released intracellularly in a self-regulated manner through acidity-triggered degradation of ACC, where DOX could amplify the ferroptosis effects of Fe2+ by producing H2O2. This nanoformulation has demonstrated potent ferroptosis efficacy and may offer clinical promise.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2015
·
IF 12.881
Kai Han,Shi-Bo Wang,Qi Lei,Jing-Yi Zhu,Xian-Zheng Zhang
Photodynamic therapy faces the barrier of choosing the appropriate irradiation region and time. In this paper, a matrix metalloproteinase-2 (MMP-2) responsive ratiometric biosensor was designed and synthesized for aggregation-induced emission (AIE)-guided precise photodynamic therapy. It was found that the biosensor presented the MMP-2 responsive AIE behavior. Most importantly, it could accurately differentiate the tumor cells from the healthy cells by the fluorescence ratio between freed tetraphenylethylene and protoporphyrin IX (PpIX, internal reference). In vivo study demonstrated that the biosensor could preferentially accumulate in the tumor tissue with a relative long blood retention time. Note that the intrinsic fluorescence of PpIX and MMP-2-triggered AIE fluorescence provided a real-time feedback which guided precise photodynamic therapy in vivo efficiently. This strategy demonstrated here opens a window in the precise medicine, especially for phototherapy.
研究领域:
癌症研究
·
治疗诊断学
·
生物医学工程
·
分子影像
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）