Analytical Cellular Pathology
·
2022
·
IF 4.133
Yingru Zhang,Yiyang Zhao,Jingwen Liu,Chunpu Li,Ying Feng,Shasha Jiang,Xiaoting Sun,Xueqing Hu,Yan Wang
Tanshinone IIA (TanIIA) is the main active ingredient in the fat-soluble components isolated from Salvia miltiorrhiza Bunge. Our previous studies have convincingly proved that TanIIA is an effective drug against human colorectal carcinoma cells. In order to further demonstrate the effect of TanIIA on CRC, we carried out exploratory research about it in vivo and in vitro. The results demonstrated that TanIIA were observably more effective than control group in preventing tumor growth, and it has increased the survival time. Cancer cells viability and proliferation were accompanied by concentration and time dependent decline reached with TanIIA. We found that TanIIA altered the morphology of cytoskeleton and it could obviously induce apoptosis of colorectal cancer cells and block the cells in the G0/G1 phase. TanIIA also increased phosphorylation of p38MAPK, upregulated ATF-2 expression and downregulated Transgelin-2 expression, which could be reversed by SB203580, a p38MAPK-specific inhibitor. Our results suggested that TanIIA could induce apoptosis of colorectal cancer and block the cells in G0/G1 phase involved in downregulating the expression of Transgelin-2 through p38MAPK signal pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-12
·
IF 3.8
Song Yang,Zhang Hui,Geng Jie,Chen Haoran,Bo Yang,Lu Xuechun
Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
高影响因子
Nanomaterials
·
2023
·Vol. 13
·期 11
·1779
·
IF 5.3
Shunyu Zhang,Jinxia Li,Liang Yan,Yue You,Feng Zhao,Jixing Cheng,Limin Yang,Yanqi Sun,Qingchao Chang,Ru Liu,Yunhui Li
Telomerase is constitutively overexpressed in the majority of human cancers and telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy. BIBR 1532 is a well-known synthetic telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of telomerase. However, water insolubility of BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive drug delivery vehicle for improved transport, release and anti-tumor effects of BIBR 1532. Herein, ZIF-8 and BIBR[email protected]were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of BIBR 1532 in ZIF-8 coupled with an improved stability of BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of BIBR 1532 with more accumulation in the nucleus. BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of cancer cells as compared with free BIBR 1532. A more potent inhibition on hTERT mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in BIBR[email protected]cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.Keywords:ZIF-8;drug loading;transport;protonation effect;telomerase inhibitor
研究领域:
药学
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癌症研究
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药物递送系统
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 2
·2211-2216
·
IF 1.692
Xuefeng Yang,Handong Huang,Maijian Wang,Xingbin Zheng,Jie Xu,Ming Xie
Nonylphenol (NP) is a well-known endocrine-disrupting chemical (EDC), which can enhance the progression of cancer by functioning as an estrogen‑like factor. In the present study, the effects of different concentrations of NP on COLO205 colorectal cancer (CRC) cells were examined. The results of flow cytometric analysis revealed that NP significantly decreased the proportion of cells in the G0/G1 phase in a dose‑dependent manner, which was accompanied by a marginal increase in the proportions of cells in S and G2/M phases. NP did not induce apoptosis, whereas estradiol (E2) did induce apoptosis. To elucidate the mechanisms underlying the action of NP on COLO205 cells, the transcriptional levels of extracellular signal‑regulated kinase (ERK)1, ERK2 and phosphoinositide 3‑kinase (PI3K) were assessed using reverse transcription‑quantitative polymerase chain reaction analysis. The expressions levels of ERK1, ERK2 and PI3K were increased by treatment with NP in a dose‑dependent manner. On examining protein levels, the expression of PI3K p38 was increased by NP and E2, and the expression of ERK1/2 was increased by NP. The phosphorylation of the ERK protein was significantly increased by treatment with NP at a high concentration (10‑4 M; P<0.01), but significantly decreased by E2 (P<0.01). Two key proteins in the transforming growth factor (TGF)β pathway (c‑Fos and SnoN) were selected for analysis using western blot analysis in the COLO205 cells treated with NP and E2. The expression levels of c‑Fos and SnoN were significantly increased by treatment with E2 (10‑7 M; P<0.01) and NP (10‑7‑10‑4 M; P<0.01). Taken together, these results indicated that NP affected the development of CRC via the ERK signaling pathway and TGFβ pathway.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Zhao Zhao,Mei Ji,Qianqing Wang,Nannan He,Yue Li
Off-target drug delivery, together with multidrug resistance (MDR), are two keys obstacles that account for the disappointing outcome in clinical chemotherapy of cancer. To solve these dilemmas, Herein, we constructed cancer cell membrane (CCM) modified silica (CS) nanoparticles (CCM/CS) to co-deliver Ca 2+ channel siRNA with doxorubicin (DOX) to construct a platform (CCM/CS/R-D) for the efficient therapy of cervical cancer. It was demonstrated that the optimal CCM/CS/R-D was spherical nanoparticles with size at 122.39 ± 4.69 nm and the surface charge of -27.76 ± 3.12 mV. In addition, the CCM/CS/R-D showed acid responsive drug release while high stability under physiological conditions with negligible hemolysis. The CCM/CS/R-D showed CCM mediated cellular uptake and efficient endosomal escape as well as siRNA transfection potential (comparable to that of PEI 25 K) on MDR cervical cancer cells (HeLa/DOX). Most importantly, the MDR of cancer cells was conquered through modulation of T-type Ca 2+ (Cav) channels. It was observed that the Cav channel siRNA could negatively regulate the level of cytosolic Ca 2+ concentration which triggered G0/G1 phase cell cycle arrest and elevated intracellular drug retention in HeLa/DOX cells without significantly affect the expression of P-glycolprotein (P-gp). The in vitro and in vivo experiments revealed that CCM/CS/R-D exerted greatly enhanced tumor targetability and therapeutic effect on HeLa/DOX, which was superior than CS/R-D or mono delivery system (CCM/CS/R or CCM/CS/D).
研究领域:
癌症研究
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纳米医学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Small
·
2016
·Vol. 12
·期 19
·2595-2608
·
IF 8.315
Yu Gao,Songen Gu,Yingying Zhang,Xiaodong Xie,Ting Yu,Yusheng Lu,Yewei Zhu,Wenge Chen,Huijuan Zhang,Haiyan Dong,Patrick J. Sinko,Lee Jia
The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima.
研究领域:
纳米技术
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癌症生物学
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Aging-US
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2019
·
IF 5.515
Yanhua Du,Jun Lin,Rulin Zhang,Wanli Yang,Heng Quan,Lijuan Zang,Yaqin Han,Bing Li,Hong Sun,Jun Wu
Globally, epithelial ovarian cancer (EOC) is the most common gynecological malignancy with poor prognosis. The expression and oncogenic roles of ubiquitin specific peptidase 5 (USP5) have been reported in several cancers except EOC. In the current study, USP5 amplification was highly prevalent in patients with EOC and associated with higher mRNA expression of USP5. USP5 amplification and overexpression was positively correlated with poor prognosis of patients of ovarian serous carcinomas. Disruption of USP5 profoundly repressed cell proliferation by inducing cell cycle G0/G1 phase arrest in ovarian cancer cells. Additionally, USP5 knockdown inhibited xenograft growth in nude mice. Knockdown of USP5 decreased histone deacetylase 2 (HDAC2) expression and increased p27 (an important cell cycle inhibitor) expression in vitro and in vivo . The promoting effects of USP5 overexpression on cell proliferation and cell cycle transition, as well as the inhibitory effects of USP5 overexpression on p27 expression were mediated by HDAC2. Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2. HDAC2 protein was positively correlated USP5 protein, and negatively correlated with p27 protein in ovarian serous carcinomas tissues. Collectively, our data suggest the oncogenic function of USP5 and the potential regulatory mechanisms in ovarian carcinogenesis.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 235
·期 4
·3612-3625
·
IF 4.522
Liming Wang,Xin Zhang,Yang Liu,Shun Xu
The pivotal roles of long noncoding RNAs have been reported in various cancers. Recently, FBXL19-AS1 was proposed to be involved in tumor progression. However, its role in lung adenocarcinoma (LUAD) remains elusive. In this study, we observed that FBXL19-AS1 was significantly upregulated in LUAD tissues and high FBXL19-AS1 expression in LUAD was associated with a poor prognosis. Nevertheless, miR-203-3p showed the opposite effect. Moreover, cell viability and apoptosis analysis revealed that FBXL19-AS1 knockdown could arrest LUAD cells in G0/G1 phase and inhibit cell proliferation, migration and invasion in vitro and inhibited LUAD tumor progress in vivo. Mechanistically, we identified FBXL19-AS1 could act as a miR-203a-3p sponge using dual-luciferase reporter assay. In addition, we demonstrated that downregulation of miR-203a-3p reversed growth inhibition of LUAD cells caused by FBXL19-AS1 knockdown. Finally, FBXL19-AS1/miR-203a-3p axis was found to associate with baculoviral IAP repeat-containing protein 5.1-A-like (survivin), distal-less homeobox 5, E2F transcription factor 1, and zinc finger E-box binding homeobox 2 to regulate metastasis in LUAD cells. This study reveals a significance and mechanism of FBXL19-AS1 in LUAD proliferation and metastasis and offers a potential prognostic marker and a therapeutic target for patients with LUAD.
研究领域:
癌症生物学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 46
·期 3
·1295-1307
·
IF 3.591
Zhi-Gang Yin,Xiong-Wei Liu,Hui-Juan Wang,Min Zhang,Xiong-Li Liu,Ying Zhou
A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds displayed good anticancer activities against four tested tumor cells (A549, PC-3, NCI-H1299, Caco-2). Among these compounds, compound 3t displayed the most potent and broad-spectrum anti-proliferative inhibition against the tested cell lines, especially A549 cells, and was more potent than arundine and cisplatin drugs, and had selectivity in cancer cells compared to MRC-5 and HK-2 normal cells. Preliminary mechanism studies showed that compound 3t exerted an anti-tumor effect in A549 cells by inhibiting the proliferation, colony formation and migration of A549 cells, and inducing cycle arrest at the G0/G1 phase and apoptosis. Furthermore, treatment of A549 cells with compound 3t caused increased ROS content and induced MMP collapse; western blot analysis showed that the expression level of p53 was significantly increased; Bax/Bcl-2 ratio and Cyt c were increased, and caspase-9, -3, and PARP were cleaved. These studies showed that compound 3t could induce apoptosis of A549 cells through the mitochondrial pathway, which was related to the activation of p53 and the generation of ROS. Thus, our results indicate that compound 3t may be used as a promising skeleton for the development of new anti-tumour drugs.
研究领域:
药物化学
·
肿瘤学
·
药学
·
细胞生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）