BREAST CANCER RESEARCH AND TREATMENT
·
2025
·Vol. 57
·期 4
·1064
·
IF 3
Jie Hu,Qilong Liu,Bi Feng,Yanling Lu,Kai Chen
Purpose Esophageal cancer (EC) is a rapidly progressing malignancy characterized by a low survival rate and limited treatment success, largely due to late-stage detection, frequent recurrence, and a high propensity for metastasis, despite ongoing advances in therapeutic strategies. While oxaliplatin (L-OHP) is a potent chemotherapeutic agent that induces apoptosis in EC cells, its effectiveness is significantly hindered by the development of resistance. Materials and Methods The assessment of gene and protein expression was conducted through a combination of quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Cell viability was assessed using the cell counting kit-8 assay. The interactions among ALYREF, TBL1XR1, KMT2E, and APOC1 were investigated through RNA immunoprecipitation, chromatin immunoprecipitation (ChIP), ChIP-reChIP, RNA pulldown, and dual-luciferase assays. An in vivo mouse model of EC was established. Results Expression levels of both APOC1 and ALYREF were elevated in L-OHP–resistant EC tissues and cell lines, and their silencing enhanced sensitivity to L-OHP. TBL1XR1 and KMT2E synergistically upregulated APOC1 expression. Moreover, ALYREF recognized the 5-methylcytosine (m5C) sites on TBL1XR1 and KMT2E mRNAs, stabilizing these transcripts and promoting APOC1 expression. The regulatory role of these interactions was further validated in vivo . Conclusion This study demonstrated that ALYREF interacted with the m5C sites on TBL1XR1 and KMT2E mRNAs, enhancing their stability and leading to increased transcription of APOC1, which in turn contributed to L-OHP resistance in EC. These findings suggest that targeting APOC1 could be a promising strategy for overcoming L-OHP resistance in EC.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Xiaofeng Liu,Chaojing Li,Fan Zhao,Robert Guidoin,Kaitai Liu,Fujun Wang,Lu Wang
Stent implantation is a widely used palliative treatment for relieving strictures in malignant esophageal cancer. However, conventional fully covered stents play a role in preventing the tumor from ingrowth but increasing the risk of migration. Therefore, there is an urgent need for a multifunctional stent that not only reduces migration but also provides synergistic therapeutic benefits to inhibit tumor growth. This study proposed a braided esophageal stent with synergistic photothermal and chemotherapy functions to achieve precise controllable drug release. The stent was braided of Nitinol fiber and polyethylene terephthalate fiber in one-step, in which Nitinol loaded with high-efficiency photothermal conversion agent gold nanoparticles and polyethylene terephthalate loaded anti-tumor drugs release mediated by a temperature-responsive coating. The stent showed anti-migration ability and orchestrated the localized hyperthermia plus thermal-stimuli drug release during the tumor lesion. Cell experiments confirmed that the stent showed a significantly synergistic tumor cell killing effect (28.29 %). In 3D tumor sphere model, the apoptosis rate of tumor cells reached 31.34 %. In summary, the composite stent design strategy integrates anti-migration features and photoheating-controlled drug release for synergistic cancer therapy, providing a new design idea for the application of nickel-titanium alloy stents in the treatment of malignant esophageal stenosis.
研究领域:
生物医学工程
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肿瘤学
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材料科学
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高影响因子
Food Science and Human Wellness
·
2019
·
IF 0
Shaokang Wang,Lingmeng Fu,Yi Wu,Hongmei Xiao,Jing Wang,Guiju Sun
The present study was conducted to verify the influence of luteolin on apoptosis of Eca109 cells and to further investigate the possible mechanisms underlying its effect on apoptosis. The cells were exposed to different concentrations of luteolin (0, 40, 80, 120, 160, 200, 240 μM) for 24, 48, and 72 h respectively. The influence of luteolin on proliferation of Eca109 cells was detected using MTT assay. Eca109 cells were then treated with luteolin (0, 40, 160, 240 μM) for 24 h. The effect of luteolin on cell cycle progression and apoptosis was assayed by using flow cytometry (FCM). Expression of caspase9 and caspase3 mRNA and protein was analyzed by real-time PCR and Western blot respectively. The results showed that luteolin could inhibit the proliferation of Eca109 cells at all concentrations in a time-dependent manner and the relative inhibition rate showed an inverted U-shaped association with the concentration of luteolin. Further, the cell cycle was arrested in the S phase following treatment with luteolin. Apoptosis analysis indicated that luteolin could induce the apoptosis of Eca109 cells across the three concentration groups, which exhibited a trend of first promotional and then inhibitory with the increases in luteolin concentration. The effect of luteolin on the mRNA and protein expression of caspase 9 and caspase3 first manifested as promotion, then inhibition. Therefore, luteolin may serve a role in promoting cell apoptosis by inducing Eca109 cell apoptosis that involves the expression of caspase3, caspase9 mRNA and protein. This study provides theoretical basis for further study and clinical application of luteolin. The specific mechanism has not yet been clarified and the other activation pathways inducing apoptosis need to be further studied.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DRUG DELIVERY
·
2017
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IF 6.402
Xiangyu Su,Chanchan Gao,Fangfang Shi,Xiaoyao Feng,Lin Liu,Ding Qu,Cailian Wang
Multidrug resistance (MDR) is the major underlying cause of the low 5-year survival rate of esophageal carcinoma. In this study, we developed a novel microemulsion system (SD-ME) co-loaded with docetaxel (DTX) and Schizandrin A, a potent chemotherapeutic agent and a potential drug resistance modulator, respectively. In the physicochemical characterization studies, SD-ME displayed a well-defined spherical shape and size (56.62 ± 4.16 nm), a narrow polydispersity index (PDI, 0.132 ± 0.002), and a negative surface charge (−19.81 ± 3.11 mv). In the cellular uptake studies, SD-ME with a DTX concentration of 30 μg/mL exhibited a 3.9-fold enhancement of DTX internalization in DTX-resistant EC109 (EC109/DDR) cells in comparison to that observed for EC109 cells, and the mechanisms were associated with reducing P-gp expression and inhibiting P-gp ATPease. The half-maximal inhibitory concentrations (IC50) of DTX and SD-ME against EC109/DDR cells were 40.57 ± 0.39 and 3.59 ± 0.06 μg/mL, respectively. Likewise, the apoptotic rate of EC109/DDR treated with SD-ME increased up to 20-fold compared to that observed with free DTX. In anticancer efficacy studies in vivo, SD-ME markedly retarded the tumor growth of nude mice bearing EC109/DDR tumor xenografts compared with D-ME and free DTX throughout the duration of study. Consequently, mice treated with SD-ME had the highest survival rate (37.5%) during the observation period (70 days). In addition, there were no apparent side effects after the administration of SD-ME. Overall, our study provides evidence for SD-ME as an effective drug delivery system for enhanced MDR tumor treatment.
研究领域:
肿瘤学
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药剂学
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分子生物学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Gaobing Ye,Shiyao Luo,Hajra Zafar,Honglei Ge,Binbin Liu,Nan Wang,Yu Jin,Miao Wang,Xu Chen,Xiaoming Ye
Esophageal cancer is one of the most common cancers in the world, ranking sixth in cancer-related mortality. Doxorubicin (DOX), as a classic broad-spectrum, non-specific small-molecular anti-tumor drug, has achieved widespread use, including in the treatment of esophageal cancer. However, due to its strong cardiotoxicity, poor tumor-targeting ability, and short half-life, the clinical application of DOX has been greatly limited. In this research, we designed and successfully synthesized a peptide sequence IEIIIK (IEK for short) with excellent pH responsiveness. Under physiological conditions (pH 7.4), the peptide can encapsulate DOX and self-assemble into a stable hydrogel (DOX-IEK) through hydrophobic and electrostatic interactions. After being injected into the acidic tumor microenvironment, the protonation degree of alkaline amino acid lysine increased and the negative charge of glutamate decreased, directly leading to enhanced electrostatic repulsion and subsequent hydrogel dissociation. Released DOX can accumulate in tumor tissue and achieve anti-tumor efficacy. More importantly, the hydrogel can act as a drug reservoir for sustained drug release, improving the drug targeting ability, prolonging the duration of drug administration to compensate for the short half-life of DOX, and reducing systemic toxicity. Ideal anti-tumor efficacy has been achieved in both the in vitro and in vivo experiments.
研究领域:
生物医学工程
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药剂学
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肿瘤学
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PubMed
高影响因子
Frontiers in Oncology
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2021
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IF 6.244
Heng Yongqing,Liang Yupei,Zhang Junqian,Li Lihui,Zhang Wenjuan,Jiang Yanyu,Wang Shiwen,Jia Lijun
The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.
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
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PubMed
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JOURNAL OF PROTEOME RESEARCH
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2024
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IF 3.8
Jijuan Zhou,Dianlong Ge,Yajing Chu,Yue Liu,Yan Lu,Yannan Chu
Detection of exhaled volatile organic compounds (VOCs) is promising for noninvasive screening of esophageal cancer (EC). Cellular VOC analysis can be used to investigate potential biomarkers. Considering the crucial role of methionine (Met) during cancer development, exploring associated abnormal metabolic phenotypes becomes imperative. In this work, we employed headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the volatile metabolic profiles of EC cells (KYSE150) and normal esophageal epithelial cells (HEECs) under a Met regulation strategy. Using untargeted approaches, we analyzed the metabolic VOCs of the two cell types and explored the differential VOCs between them. Subsequently, we utilized targeted approaches to analyze the differential VOCs in both cell types under gradient Met culture conditions. The results revealed that there were five/six differential VOCs between cells under Met-containing/Met-free culture conditions. And the difference in levels of two characteristic VOCs (1-butanol and ethyl 2-methylbutyrate) between the two cell types intensified with the increase of the Met concentration. Notably, this is the first report on VOC analysis of EC cells and the first to consider the effect of Met on volatile metabolic profiles. The present work indicates that EC cells can be distinguished through VOCs induced by Met regulation, which holds promise for providing novel insights into diagnostic strategies.
研究领域:
肿瘤学
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代谢组学
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医学检测
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Journal of Taibah University for Science
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2024
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IF 2.8
Lingyu Wang,Ruolan Li,Meiyan Li,Jiayi Sun,Jia Liu,Min Xie,Yunhui Chen,Songqi Tang
This study aimed to investigate the inhibitory effect of Zuojin Pill (ZJP) on KYSE 150 cells and xenograft tumours of the digestive tract cancer – esophageal cancer (EC) and its underlying mechanism. Initially, in vivo research demonstrated that oral administration of ZJP effectively inhibited the growth of EC tumours, and in vitro studies revealed that ZJP suppressed the proliferation, migration, and invasion of cells. Then, network pharmacology prediction identified the core target, active ingredient, and involvement of the PI3K-Akt signalling pathway in ZJP treatment of EC. Cell studies validated that ZJP affected the expression of core targets, and its active ingredients inhibited the proliferation of cells. Additionally, ZJP was shown to induce cell apoptosis, decrease mitochondrial membrane potential, and increase the level of intracellular oxidative stress. Further experimental verifications suggested that the inhibitory effects of ZJP on EC might be attributed to the modulation of PI3 K/Akt signalling pathways.
研究领域:
肿瘤学
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药理学
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分子生物学
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高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Lian Deng,Xiongjie Zhu,Zhongjian Yu,Ying Li,Lingyu Qin,Zhile Liu,Longbao Feng,Rui Guo,Yanfang Zheng
Background Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.
研究领域:
纳米医学
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肿瘤学
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药学
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分子生物学
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PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2025
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IF 4.7
Hafiz Muhammad Bilal Akram,Yulin Liu,Jianshu Dong,Xueke Zhao,Lidong Wang,Wen Zhao,Hongmin Liu,Liying Ma,Cong Han
Esophageal cancer has been regarded as a serious malignancy due to its poor prognosis and high mortality rate. Serine hydroxymethyltransferase 2 (SHMT2) is emerging as an attractive target for esophageal cancer therapy. Compound W478 was identified as a potent SHMT2 inhibitor with an IC 50 value of 1.21 μM, especially whose chemical structure is distinct from the reported SHMT2 inhibitors. Both cellular thermal shift assay and isothermal titration calorimetry experiments showed that compound W478 tightly bound to SHMT2 (K D = 10.6 ± 1.2 μM). The molecular docking analysis revealed its binding at the folate binding site of SHMT2. Moreover, compound W478 exhibited a significant antiproliferative effect on human esophageal cancer cell lines, KYSE-450 and KYSE-70 cells (IC 50 = 1.62 μM, 1.18 μM, respectively). The wound healing and transwell assays showed that compound W478 could inhibit the migratory and invasive potential of KYSE-450 and KYSE-70 cells in a dose-dependent manner. Further studies demonstrated that compound W478 could induce cell arrest at the G2/M phase and promote cell apoptosis and ROS production in KYSE-450 and KYSE-70 cells. These findings indicated that compound W478 could serve as a promising lead compound for the development of SHMT2 inhibitor to address esophageal carcinoma.
研究领域:
肿瘤学
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分子生物学
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药物化学
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转化医学
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细胞生物学
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高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2024
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IF 4.8
Suizhi Cheng,Jin Chen,Qianhui Li,Yuhong Nie,Ting Ni,Caiting Peng,Xi Luo,Yasin Pazilat,Shumin Zhang,Jiancai Tang,Zhenzhong Liu
Recent research has revealed that N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) constitutes a significant risk factor in the development of esophageal cancer. Several investigations have elucidated the beneficial impact of folic acid (FA) in safeguarding esophageal epithelial cells against MNNG-induced damage. Therefore, we hypothesized that FA might prevent MNNG-induced proliferation of esophageal epithelial cells by interfering with the PI3K/AKT/mTOR signaling pathway. In vivo experiments, we found that FA antagonized MNNG-induced proliferation of rat esophageal mucosal epithelial echinocytes and activation of the PI3K/AKT/mTOR signaling pathway. In our in vitro experiments, it was observed that acute exposure to MNNG for 24 h led to a decrease in proliferative capacity and inhibition of the PI3K/AKT/mTOR signaling pathway in an immortalized human normal esophageal epithelial cell line (Het-1A), which was also ameliorated by supplementation with FA. We successfully established a Het-1A-T-cell line by inducing malignant transformation in Het-1A cells through exposure to MNNG. Notably, the PI3K/AKT2/mTOR pathway showed early suppression followed by activation during this transition. Next, we observed that FA inhibited cell proliferation and activation of the PI3K/AKT2/mTOR signaling pathway in Het-1A-T malignantly transformed cells. We further investigated the impact of 740Y-P, a PI3K agonist, and LY294002, a PI3K inhibitor, on Het-1A-T-cell proliferation. Overall, our findings show that FA supplementation may be beneficial in safeguarding normal esophageal epithelial cell proliferation and avoiding the development of esophageal cancer by decreasing the activation of the MNNG-induced PI3K/AKT2/mTOR signaling 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
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药理学
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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2018
·Vol. 392
·期 2
·177-187
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IF 2.238
Qiao Zhe,Cheng Yao,Liu Shiyuan,Ma Zhenchuan,Li Shaomin,Zhang Wei
Casticin, a flavonoid isolated from Vitex species, has been found to have anti-tumor property in multiple human cancers. The present study aimed to investigate the effect of casticin on the proliferation and apoptosis of esophageal cancer (EC) cells, and further illustrate the underlying mechanisms. In in vitro studies, human EC cell lines TE-1 and ECA-109 were treated with various concentrations of casticin (low-, middle-, and high-dose groups). The results showed that casticin dose-dependently inhibited the proliferation and clonogenicity of EC cells and induced cell cycle arrest in sub-G1 and G2 phases. Furthermore, casticin markedly enhanced EC cell apoptosis as detected by flow cytometry and Hoechst 33342 staining. The level of anti-apoptotic Bcl-2 protein was decreased, while the levels of pro-apoptotic Bax, cleaved-caspase-3, cleaved-caspase-9, and cleaved-PARP were conversely increased in casticin-treated TE-1 and ECA-109 cells. Moreover, casticin decreased the mitochondrial membrane potential and increased the release of mitochondrial cytochrome C into cytoplasm. In addition, the JNK signaling pathway was involved in casticin-medicated anti-proliferation and pro-apoptosis. Cells pretreated with SP600125, a JNK pathway inhibitor, partially abolished the effect of casticin. Finally, the anti-tumor property of casticin was confirmed in in vivo xenograft models. Overall, we provided both in vitro and in vivo evidences that casticin inhibited the proliferation and induced apoptosis of EC cells, and the anti-tumor action of casticin was mediated, in part, by the mitochondrial-dependent apoptosis and the activation of JNK signaling 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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PubMed
高影响因子
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