DYES AND PIGMENTS
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2021
·
IF 4.889
Yun-Yun Quan,Lanlan Fan,Hongyan Shen,Binbin Wu,Shanshan Kong,Yanshu Luo,Zu-Sheng Huang,Xiaoxia Ye
Development of multifunctional probes that can be simultaneously utilized for both efficient hydrogen sulfide detection and photodynamic therapy in cancer cells is in high demand but remains worldwide challenge. Herein, a fluorescent probe DB2T based on a BODIPY structure for H 2 S fluorescence “turn-on” detection together with light sensitive anticancer capacity has been designed and synthesized. The probe DB2T features high selectivity towards H 2 S, excellent low detection limit (6.39 nM), and good biocompatibility . Importantly, the probe DB2T has been satisfactorily applied in fluorescence imaging of exogenous H 2 S in zebrafish, and successfully employed in fluorescence imaging of endogenous H 2 S in HCT116 cell and tumor tissues. Moreover, evaluation of the phototherapy effect demonstrates that the probe DB2T performs well as a photosensitizer for photodynamic ablation of HCT116 cancer cells upon white light irradiation. This work should facilitate significant advances in rational design of fluorescence systems for H 2 S detection and even in the diagnosis and treatment of H 2 S related diseases.
研究领域:
生物化学
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肿瘤学
·
药物开发
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DOI
高影响因子
RSC Medicinal Chemistry
·
2024
·
IF 4.1
Ji-Chao Guo,Shi-Hui Deng,Shu-Min Zhou,Xuan Zhou,Jiajia Du,Si-Han Zhou,Qi-Hua Zhao,Zhong-Yan Cai,Xiaoxia Ren,Ming-jin Xie
There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 μg mL−1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2015
·Vol. 12
·期 1
·192-198
·
IF 1.554
Jinpeng Li,Hao Liu,Jieping Yu,Honggang Yu
Doxorubicin (Dox) is a commonly used chemotherapeutic drug in human colon cancer. However, it becomes increasingly ineffective with tumor progression, the underlying mechanism of which remains to be elucidated. Emerging evidence has led to the identification of an association between chemoresistance and the acquisition of epithelial‑mesenchymal transition (EMT) in cancer. However, it remains to be elucidated whether this process is involved in the development of resistance to Dox in colon cancer. In HCT116 human colon cancer cells treated with Dox (50 nmol/l), EMT was induced, and transforming growth factor (TGF)β signaling and multi‑drug resistant plasma membrane glycoprotein levels were significantly increased. By contrast, silencing of Smad4, using stable RNA interference, inhibited TGFβ signaling, reversed the process of EMT and markedly increased the sensitivity of HCT116 cells to Dox. The results of the present study suggested that the combination of Dox with the downregulation of TGFβ signaling may be a potential novel therapeutic strategy with which to overcome chemoresistance during colon cancer chemotherapy.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Ruige Yang,Xiangjing Fu,Jiangping Fan,Tingting Wang,Jian Song,Ting Xu,Yong Guo,Sai-Yang Zhang
Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC 50 value of 6.1 μmol/L, superior to the reference drug 5-fluorouracil (IC 50 : 9.63 ± 0.27 µmol/L). The structure–activity relationships (SARs) indicated that the introduction of –(4-NO 2 )Ph, 3-pyridyl, –(2-F)Ph, –(4-F)Ph, –(3-F)Ph, –(4-Cl)Ph, and –(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.
研究领域:
药理学
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Si-Han Zhou,Rui-Dong Wang,Tian-Tian Wu,Shi-Hui Deng,Ji-Chao Guo,Shu-Min Zhou,Xuan Zhou,Jiajia Du,Qi-Hua Zhao,Xiaoxia Ren,Ming-jin Xie
As many of the disadvantages of traditional single therapy can be avoided with combination therapy, combination therapy has become a new treatment method. Herein, a long rod-shaped gallium composite multifunctional material (CP–Au-PEG-FA@BSA@IR780) based on chemotherapy therapy (CT), photothermal therapy (PTT) and photodynamic therapy (PDT) is constructed to increase reactive oxygen species (ROS) levels and Au NP release. CP-Au-PEG-FA@BSA@IR780 has fluorescence localization characteristics and can combine with CT-DNA to cause cancer cell apoptosis. The in vitro cytotoxicity experiments showed the excellent biocompatibility and great therapeutic efficacy of the designed nanoplatform compared to those of the IR780 group, which had weak red fluorescence. The in vivo experiments also showed that the designed micro/nano platform can effectively eliminate HCT116 tumors by allowing the temperature of the tumor site to exceed 55 °C (thermal ablation) under light irradiation . The main mechanism of chemotherapy indicated that the presence of Fe 2+ /Fe 3+ can disrupt the rod-shaped structure of the original material and increase the content of Ga 3+ . Overall, CP-Au-PEG-FA@BSA@IR780 is a promising cancer therapy strategy that combines CT, PTT, and PDT and provides new insights into the synthesis method of enhancing composite materials with photothermal properties.
研究领域:
肿瘤学
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纳米医学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Kemin Mao,Xianghong Wang,Yakun Hou,Xiaowei He,Shuo Geng,Faizan Ahmed Sadiq,Yunhe Lian,Yaxin Sang
Equol is an isoflavone-derived metabolite known to exhibit strong estrogenic and antioxidant activities. The aim of this paper is twofold: first, to confirm the anticancer potential of equol against colorectal cancer, and second, to reveal the underlying mechanisms. After treatment with 40 μg/mL equol, cell proliferation, cell migration, and colony formation of HCT116 colon cancer cells were inhibited. Network pharmacology and transcriptomics analysis revealed the downregulation of genes related to DNA replication (CCND1, E2F1, CDC6, CDC45, MCM4), leading to G1/S cell cycle arrest and the induction of cell apoptosis, which was confirmed by flow cytometry. Genes associated with the G2-to-M transition (CDK1, CCNA2, CCNB1) were also downregulated. In addition, equol downregulated genes (FOXM1 and ASPM) that control cell migration and invasion. Our data indicate that equol can inhibit colorectal cancer by targeting multiple pathways, suggesting its potential as a key component in the adjuvant treatment of colorectal cancer.
研究领域:
药理学
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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
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2019
·Vol. 66
·期 5
·787-793
·
IF 1.559
Li Tao,Ying Gu,Jian Zheng,Jinkun Yang,Yingjie Zhu
Evidence suggests that Weichang'an (WCA) inhibited the metastasis of colorectal cancer (CRC) in vitro and downregulates oncogenic β-catenin; more intriguingly, we also found an upregulation of ARHGAP25 in this process. This study aimed to investigate the mechanisms by which WCA regulated CRC metastasis in vitro . Here, HCT116 cells were transfected with siRNAs to interfere ARHGAP25 expression. WCA decoction, XAV939 (a specific Wnt/β-catenin pathway inhibitor), and LiCl (an activator for Wnt/β-catenin pathway) were used for treatment. Cell migratory and invasive capacities were determined using Transwell chamber. The activation of Wnt/β-catenin pathway was assessed by determining the expression of MMP7, MMP9, ZEB1, and β-catenin. The study suggests that WCA inhibited the migration and invasion of HCT116 cells and suppressed the activation of Wnt/β-catenin pathway, as evidenced by retarding MMP7, MMP9, ZEB1, and β-catenin. However, siRNA–ARHGAP25 resulted in the opposite. In siRNA–ARHGAP25-transfected HCT116 cells, WCA (0.4 mg/mL) induced the antimetastatic effects and the inactivation of Wnt/β-catenin pathway was remarkably reversed with additional LiCl treatment. Our study concludes that inhibiting Wnt/β-catenin pathway while promoting ARHGAP25 was the mechanism, whereby WCA retarded migration and invasion of CRC in vitro .
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Asian Pacific Journal of Cancer Prevention
·
2014
·Vol. 15
·期 13
·5201-5205
·
IF 1.5
Xie Mei-Juan,Ma Yi-Hua,Miao Lin,Wang Yan,Wang Hai-Zhen,Xing Ying-Ying,Xi Tao,Lu Yuan-Yuan
Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Letters in Drug Design & Discovery
·
2026
·
IF 1.6
Lijiao Luo,Hui Wang,Changxue Li
Background Oxaliplatin (OXP) resistance and an immunosuppressive microenvironment are major hurdles in colorectal cancer (CRC) treatment. This study developed a biomimetic "Trojan Horse" nanoplatform (CCM@CONPs) to systematically elucidate its therapeutic efficacy and mechanisms in overcoming these barriers. Methods A biomimetic delivery system was engineered by cloaking OXP/Celecoxib (CXB)-loaded methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) micelles with HCT116 cancer cell membranes. Physicochemical characterization and homologous targeting capabilities were assessed. The synergistic molecular mechanisms regarding cyclooxygenase-2 (COX-2) inhibition, DNA damage, immunogenic cell death (ICD), and subsequent pro-inflammatory cytokines secretion were investigated in vitro. In vivo anti-tumor efficacy, immune activation profiles, and biosafety were evaluated in CRC xenograft models. Results The study successfully fabricated CCM@CONPs with a uniform core-shell structure and excellent stability. The biomimetic coating conferred precise homologous targeting, resulting in significantly enhanced cellular uptake compared to non-coated micelles. Mechanistically, co-delivered CXB functioned as a sensitizer by abrogating the COX-2 signaling axis, which potentiated OXP-mediated genotoxicity and downregulated DNA repair mechanisms. This precise "seek-and-destroy" strategy amplified OXP-induced ICD and significantly stimulated the secretion of pro-inflammatory cytokines (such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) in vitro, indicating its robust potential to alleviate local immunosuppression. In vivo evaluations further demonstrated that CCM@CONPs achieved superior tumor growth inhibition with negligible systemic toxicity. Conclusion This study suggests that CCM@CONPs exerts potent anti-cancer effects in CRC via active homologous targeting and mechanism-based molecular sensitization. By effectively mitigating tumor defense networks and promoting pro-inflammatory immune responses, this bio-inspired platform provides a highly translational and valuable framework for advancing precision chemo-immunotherapy in refractory CRC.
✓ 已验证
DOI
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2018
·Vol. 47
·期 4
·1667-1681
·
IF 5.5
Lan Ying,Li Xiulian,Liu Xuebo,Hao Cui,Song Ni,Ren Sumei,Wang Wei,Feng Ningchuan,Zhang Lijuan
Background/Aims: Genistein is a natural isoflavone enriched in soybeans. It has beneficial effects for patients with mucopolysaccharidose type III through inhibiting glycosaminoglycan biosynthesis. However, other studies indicate that genistein does not always inhibit glycosaminoglycan biosynthesis. Methods: To understand the underlying molecular mechanisms, CHOK1, CHO3.1, CHO3.3, and HCT116 cells were treated with genistein and the monosaccharide compositions and quantity of all glycans from the cell lysate were measured after thorough acid hydrolysis followed by HPLC analysis. In addition, the glycosaminoglycan disaccharide compositions were obtained by stable isotope labeling coupled with LC/MS analysis. Results: Genistein treatment reduced the amount of glycans but increased the amount of glycosaminoglycans in HCT116 cells. In contrast, genistein treatment reduced both glycan and glycosaminoglycan quantities in CHOK1, CHO3.1, and CHO3.3 cells in addition to differential changes in glycosaminoglycan disaccharide compositions. Conclusion: Genistein treatment reduced overall glycan quantity but glycosaminoglycan quantities were either increased or decreased in a cell type-dependent manner
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 4
·4177-4184
·
IF 1.664
Zhengting Chen,Xinyi Cai,Li Chang,Yaoxiong Xia,Li Wang,Yu Hou,Lan Li,Dingguo Pan,Furong Li,Shan Liu,Wei Xiong,Wenhui Li
Concurrent radiotherapy and chemotherapy is a widely used, comprehensive treatment for rectal cancer. By studying the impact of concurrent chemoradiotherapy on the invasion and migration of colorectal cancer (CRC) cells and researching the associated molecular mechanisms, the present study aimed to provide a novel method to improve the therapeutic effect of this treatment against CRC. Human HCT116 and HT29 CRC cells were simultaneously treated with 4 Gy of 6 MV X‑rays and 10 µmol/l 5‑fluorouracil to establish a residual cell model. Transwell migration and invasion experiments were used to analyse the invasion and migration of the cells. The expression of long non‑coding (lnc)RNAs was detected using a gene chip, and reverse transcription‑quantitative polymerase chain reaction analysis was used to determine lncRNA expression levels. Specific small interfering RNAs were transfected into HCT116 residual cells to silence the expression of the identified key genes. The migration and invasion of residual CRC cells were demonstrated to be significantly increased compared with the original cells. Pvt1 oncogene, long‑chain non‑protein‑coding RNA 152 (LINC00152), and MIR22 host gene were selected as potential targets. However, the migration and invasion of residual HCT116 cancer cells were only significantly decreased following silencing of LINC00152 expression. LINC00152 may therefore be a potential biomarker involved in modulation of the biological characteristics of residual CRC cells following chemoradiotherapy.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Yiqun Xia,Jundixia Chen,Yun Yu,Fengjiao Wu,Xin Shen,Chenyu Qiu,Tingting Zhang,Lin Hong,Peisen Zheng,Rongrong Shao,Chenxin Xu,Fang Wu,Wei Chen,Congying Xie,Ri Cui,Peng Zou
Background: Cancer is a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that inhibit oncogenic signaling pathways. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of many cancers. Several mTOR inhibitors are approved for the treatment of cancers. However, the anticancer efficacies of mTOR inhibitor monotherapy are still limited. Methods: Western blot was used to detect the expression of indicated molecules. Thioredoxin reductase (TrxR) activity in cells was determined by the endpoint insulin reduction assay. Immunofluorescence staining was used to analyze precise location and expression of target proteins. Nude mice were used for xenograft tumor models. Results: We identified a synergistic lethal interaction of mTOR and TrxR inhibitors and elucidated the underlying molecular mechanisms of this synergism. We demonstrated that mTOR and TrxR inhibitors cooperated to induce cell death by triggering oxidative stress, which led to activation of autophagy, endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK) signaling pathway in cancer cells. Remarkably, we found that auranofin (AF) combined with everolimus significantly suppressed tumor growth in HCT116 and SGC-7901 xenograft models with no significant signs of toxicity. Conclusion: Our findings identify a promising therapeutic combination for cancer and has important implications for developing mTOR inhibitor-based combination treatments.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 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）