International Journal of Biological Sciences
·
2019
·
IF 4.067
Peihai Cao,Yiqun Xia,Wei He,Tingting Zhang,Lin Hong,Peisen Zheng,Xin Shen,Guang Liang,Ri Cui,Peng Zou
Colon cancer is a malignant type of cancer with high prevalence and is one of the primary causes of cancer-related deaths. Oxaliplatin plays a significant role in the treatment of cancer, but the application of oxaliplatin is restricted due to its toxic side effects and drug resistance in clinical practice. Therefore, there is an urgent need for new strategies that can synergize with oxaliplatin for confronting colon cancer. Alantolactone (ALT), a natural sesquiterpene lactone, possesses antitumor properties in a number of cancer cell lines. In the present study, we investigated how ALT acts synergistically with oxaliplatin on human colorectal cancer HCT116 and RKO cells in vitro and in vivo . We observed that ALT strengthened the effect of oxaliplatin-induced growth restrain and apoptosis in HCT116 and RKO cells. It is through a mechanism concerning remarkable accumulation of intracellular reactive oxygen species (ROS) and activation of JNK and p38 MAPK signaling pathways. These changes ultimately induced apoptosis of HCT116 and RKO cells. Pretreatment of cells with the ROS reversal agent NAC significantly blocked the apoptosis induced by the combination treatment, and suppressed expression of JNK and p38 phosphorylation in HCT116 and RKO cells. In the xenograft model, the combination therapy displayed stronger antitumor activity compared with single agents. Immunohistochemistry of subsequent treatment tumors showed a significant decrease in proliferation as compared to either of the treatments alone. These results suggest that the combination treatment with ALT and oxaliplatin may become a potential therapeutic strategy for colon cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Basharat Ali,Muhammad Riaz,Ajmal Khan,Nadir Rasheed,Muhammad Masood,Ali Iftikhar,Amir Faisal,Sobia Ahsan Halim,Jalal Uddin,Afnan Jan,Ahmed Al-Harrasi
Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides ( 2−13 ) were synthesized and characterized using Electron Ionization Mass Spectrometry (EI-MS), proton and carbon-13 nuclear magnetic resonance ((Singhal et al., 2013 [ 1 ] ) HNMR, and 13 C NMR), Infrared (IR), and elemental analysis. The anticancer activity of the carbothioamide derivatives ( 2–13 ) was measured in the HCT116 colorectal cancer cell line by means of a three day sulforhodamine B (SRB) proliferation assay. Among the series, four compounds ( 2 , 4 , 11 , and 12 ) which inhibited the cell viability by more than 50 % at 50 μM concentration. IC 50 determination of these four compounds revealed 1-benzoyl-4-(2-bromophenyl) thiosemicarbazide ( 11 ) as the most potent compound with IC 50 values of 21.61 ± 4.77 μM, 18.34 ± 3.53 μM and 17.87 ± 12.02 μM in the breast cancer (MCF-7) cell line, human colorectal carcinoma (HCT116) cell line and MD Anderson-metastatic breast (MDA-MB-453) cell lines respectively. Prolonged treatment of cells with the compound resulted in apoptotic cell death as determined by cleavage of Poly (ADP-ribose) polymerase (PARP), a caspase 3 substrate and an apoptotic marker. This study, therefore, explored novel derivatives of carbothioamides for their anticancer activities; the structure activity relationship (SAR) reported in this study and predicted docking analysis and ADMET profile will help optimize carbothioamides as anticancer agents.
研究领域:
药物化学
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药理学
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肿瘤学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
CELL TRANSPLANTATION
·
2021
·
IF 4.064
Xiao-Yu Chen,Sheng-Yong Yang,Xiao-Jie Ruan,Hong-Yue Ding,Ning-Xi Wang,Fang Liu,Jia-Chu Li,Yi Li
Methionine sulfoxide reductase B1 (MsrB1) can catalyze both free and protein-bound R-methionine sulfoxides (R-MetO) to methionine (Met). It has been reported that MsrB1 plays an important role in the development of HCC and human bone osteosarcoma. However, little is known about the functions of MsrB1 in human colorectal cancer (CRC). Herein, we detected MsrB1 expression level in CRC tissue and cell lines, and investigated the effect of MsrB1 knockdown on CRC phenotypes and possible mechanisms involved in. The results showed that MsrB1 was highly expressed in both CRC tissues and cell lines, and that cell proliferation, migration and invasion were significantly inhibited, but apoptosis was increased after MsrB1 knockdown in colorectal cancer HCT116 and RKO cell lines, compared to control siRNA group. In addition, E-cadherin protein level was increased, vimentin and Snail protein were greatly decreased after knockdown of MsrB1 in cells. Furthermore, pGSK-3β (Ser9) and β-catenin protein levels were reduced, the promoter activity of TCF/LEF construction was inhibited after MsrB1 knockdown in cells, suggesting that GSK-3β/β-catenin signaling axis was involved in the tumorigenesis of CRC. In conclusion, the oncogenic role and related mechanisms of MsrB1 in CRC discovered in our work determined the potential role of MsrB1 as a biomarker and may provide a new target for clinical therapy of CRC.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2020
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IF 7.242
Xinxin Li,Lin Liu,Yu Fu,Hongda Chen,Murad M.A. Abualrejal,Hua Zhang,Zhenxin Wang,Huimao Zhang
Currently, it is still a great challenge to develop tumor targeting nanoparticles with high sensitivity and high resolution for improving the non-invasive detection ability of colorectal cancer (CRC) at an early stage. In this study, NaErF 4 : [email protected] 4 :Yb [email protected] upconversion nanoparticles (UCNPs) were prepared with high upconversion luminescence (UCL) emission in red light region through adjusting the doping ratios of Er and Yb elements in the core. For biomedical applications, the carboxyl-terminated silica shell was introduced to transfer the as-prepared UCNPs from the organic phase to the aqueous phase, and allowed conjugation with peptide ligands derived from the l -SP5 peptide ( i.e. , l -SP5-H and l -SP5-C), respectively. Due to the tumor-targeting affinity of the PSP motif in the peptide ligands, the as-prepared peptide functionalized UCNPs ( [email protected] 2 - l -SP5-H and [email protected] 2 - l -SP5-C) can be used as an active tumor targeting contrast agents for UCL/T 1 -weighted magnetic resonance (MR) dual-mode imaging. Both the in vitro and in vivo experimental results demonstrated that [email protected] 2 - l -SP5-C has relatively high affinity for the HCT116 CRC subtype. Moreover, [email protected] 2 - l -SP5-C can visualize ultra-small subcutaneous xenografted HCT116 tumors (c.a. 13 mm 3 in volume) by in vivo UCL imaging. Statement of Significance 1. High red emission UCNPs were synthesized for tumor-targeting dual-mode bioimaging. 2. With tumor-binding affinity peptide, [email protected] 2 - l -SP5-C shows high HCT116 tumor targeting ability. 3. [email protected] 2 - l -SP5-C successfully achieves sensitive detection of ultrasmall HCT116 tumors.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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分子成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Yun-shan Wei,Kun Feng,Hong Wu
In order to modify colonic release behavior of lactoferrin (Lf), a hydrophobic composite nanofibrous carrier (CNC) was constructed by emulsion coaxial electrospinning. Ethylcellulose/pectin based water-in-oil emulsion and Lf-contained polyvinyl alcohol solution were used as shell and core fluids, respectively. An electrospinning diagram was first constructed to screen out suitable viscosity (51–82 cP) and conductivity (960–1300 μS/cm) of the dispersed phase of pectin solution for successful electrospinning of shell emulsion. Varying mass fraction of pectin solution (5 %–20 %) of shell emulsion during emulsion coaxial electrospinning obtained CNCs with different micro-structures, labeled as 5&95 CNC, 10&90 CNC, 15&85 CNC, 20&80 CNC. These CNCs all achieved colonic delivery of Lf (>95 %), and the time for complete release of Lf in simulated colon fermentation process were 10, 7, 5 and 3 h, respectively. That is, the greater the pectin content in CNC, the faster the release rate of stabilized Lf in colon. Lf release in simulated colon fermentation fluid involved complex mechanisms, in which diffusion release of Lf was dominant. Increasing colonic release rate of Lf enhanced its regulation effect on the expression levels of cell cycle arrest and apoptosis-related protein and promote its effective inhibition on the proliferation of HCT116 cell.
研究领域:
药剂学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2021
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IF 3
Dou-Dou XU,Xiao-Ying HOU,Ou WANG,Di WANG,Dan-Ting LI,Si-Yuan QIN,Bo LV,Xiao-Min DAI,Zun-Jian ZHANG,Jian-Bo WAN,Feng-Guo XU
Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF- α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E i, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo . As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.
研究领域:
药理学
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肿瘤学
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中医
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2018
·Vol. 41
·期 8
·1243-1250
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IF 1.694
Yunpeng Qi,Renping Wang,Liang Zhao,Lei Lv,Fan Zhou,Tian Zhang,Feng Lu,Hongli Yan,Gengli Duan
Celastrol is well known for its anti-cancer effects, yet its specific mechanisms against colon cancer are still not fully elucidated. In this study, cytotoxic effect of celastrol against HCT116 colon cancer cells was investigated based on cell viability assay and flow cytometry assay, and the possible mechanism was explored using a strategy combining metabolic profiling and targeted metabolite analysis based on ultra performance liquid chromatography (UPLC)/MS. Celastrol was found to inhibit the growth of colon cancer cells and induce apoptosis. Metabolomics analysis revealed characteristic changes in metabolic profiles of the colon cancer cells, revealing altered levels of amino acids, carnitine, and lipid markers. Most interestingly, with the assistance of targeted metabolite analysis, tryptophan (Trp) level was significantly increased whereas kynurenine (Kyn) level was decreased in colon cancer cells after celastrol treatment, together with markedly declined Kyn/Trp ratios. Western blot analysis revealed that expression of indoleamine 2,3-dioxygenase (IDO), the enzyme catalyzing Trp to generate Kyn, was dramatically inhibited in colon cancer cells after celastrol treatment, with a dose-dependent manner. These results suggest that suppression of IDO expression and tryptophan catabolism may be part of the mechanisms of celastrol in its cytotoxic effect against HCT116 colon cancer cells. This study provided scientific basis for further development of celastrol on treating colon cancer.
研究领域:
肿瘤学
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药理学
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代谢组学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
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IF 7.033
Xin Zhang,Yang Zhang,Ning Wang,Yetong Shen,Qing Chen,Lu Han,Bo Hu
NCs (1:1:4, 6 μL) to synergistically reduce the viability of HCT116 cells to 15.63± 2.90%.Conclusion: By using NIR-irradiation, the “transitive” nanoheaters can remotely control the activity of both bacteria (germinated from spore) and cancer cells. This discovery provides basis and a feasible plan for controllable safer treatment of bacteria therapy, especially anaerobes with spores in hypoxic areas of the malignant solid tumors.
研究领域:
癌症研究
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生物医学工程
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纳米技术
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治疗递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2023
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IF 7.3
Ben Yi,Shuai Zhang,Suying Yan,Yanfei Liu,Zhiqiang Feng,Tianhao Chu,Jun Liu,Wei Wang,Jun Xue,Chunze Zhang,Yijia Wang
Introduction Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear. Method We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors. Results Under single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models. Conclusions Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.
研究领域:
肿瘤学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Wei Zhao,Siying Huang,Minlan Li,Xiao–kun Ouyang,Junhong Ling
Fucoxanthin (FX) is a hydrophobic drug with potential antitumor activity. The main challenge with using fucoxanthin as a therapeutic agent is its low bioavailability and poor physicochemical stability. To overcome these limitations, we designed a pH-targeted delivery system using alginate oligosaccharide-encapsulated aminated mesoporous silica (nMSN-FX-ALG). The drug release experiments indicated that nMSN-FX-ALG exhibited a high drug delivery efficiency. Under physiological environment at pH 5.5, the cumulative release rate of FX from nMSN-FX-ALG system reached 73.6% after 24 hours, demonstrating its pH-responsive drug release capability. This confirmed that nMSN-FX-ALG could achieve targeted drug release in tumor cells. Meanwhile, nMSN-FX-ALG markedly enhanced the inhibitory effect on HCT116 cells, reducing cell viability to 50%. Furthermore, the system exhibited a notable therapeutic effect, suggesting its potential for tumor treatment. This research provides valuable insights and guidance for the targeted delivery of fucoxanthin, offering promising prospects for its application in the field of tumor treatment.
研究领域:
药学
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纳米技术
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癌症研究
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Zehao Li,Jianchao Li,Dazhuang Wang,Cong Li,Kexin Zhang,Lihong Wang,Chao Shen,Zhihang Li,Yating Ji,Lijiang Chen
In order to construct an oral drug delivery system to improve the bioavailability of drugs. This project prepared a compound drug carrier that combines the advantages of biological carriers and synthetic carriers. This oral drug delivery system (YP-MPA-ZnO-DOX) consists of yeast microcapsules (YP) and DOX-loaded ZnO nanoparticles modified with 3-mercaptopropionic acid (MPA). The average particle size of the particles was 4620 nm and the potential was about +22.7 mV as measured by particle size and zeta potential. The in vitro release experiments showed that the DOX release rate of YP-MPA-ZnO-DOX in simulated gastric fluid (SGF) for 11 h was about 20 %. The cumulative release rate of DOX in simulated intestinal fluid (SIF) for 11 h was about 10 %, indicating that YP-MPA-ZnO-DOX could resist gastrointestinal fluid erosion and had drug retention effects. Meanwhile, in the simulated tumor environment, the cumulative release of DOX could reach 97.6 %, almost completely released. Cellular experiments demonstrated that the inhibition rate of YP-MPA-ZnO-DOX on HepG2 and HCT116 cells was close to 75 % after 48 h, which was much higher than that of DOX alone. Pharmacokinetic studies demonstrated that compared with free DOX, the half-life of YP-MPA-ZnO-DOX could be prolonged to 13.621 ± 0.09 h, which significantly improved the bioavailability of DOX after oral administration. Utilization after oral administration of DOX. In conclusion, YP-MPA-ZnO-DOX provides a promising application for oral DOX.
研究领域:
药剂学
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纳米技术
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癌症研究
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）