Discover Oncology
·
2024
·Vol. 15
·期 1
·1-13
·
IF 2.8
Yin Xiaoyan,Zhang Haizhong,Wang Jingmiao,Bian Yanrui,Jia Qiaojing,Yang Zhichao,Shan Chunguang
In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.
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
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
·
2025
·
IF 1.6
Shaohao Luo,Yunfei Bai,Boqian Wang,Haixia Xu,Shu Zhang,Gang Guo,Xin Li,Hongyang Sun,Xiaobo Cui
Homeobox A1 (HOXA1) is implicated in the progression of various cancers, but its biological function in laryngeal cancer (LC) remains undefined, which is the foothold of our study. Bioinformatics analysis and survival analysis were performed to predict HOXA1 expression in LC tissues, and the prognostic relationship between high HOXA1 expression and LC. Whether high HOXA1 expression correlated with the clinical characteristics and prognosis of LC patients was analyzed. LC cell viability and sensitivity to cisplatin were determined by Methyl thiazolyl tetrazolium assay. The cell migration, invasion, and cell cycle after transfection were examined by Wound healing, Transwell, and flow cytometry assays, respectively. The corresponding mRNA and protein expressions were measured by quantitative real-time PCR or Western blot. A higher expression of HOXA1 was detected in LC tissues, which was found to be relevant to poor prognosis of LC patients. The association of high expression of HOXA1 with lymph node and clinical stage was also confirmed. Silencing of HOXA1 in LC cells enhanced the cell sensitivity to cisplatin, inhibited viability, migration, invasion and cell cycle, and reduced N-Cadherin, Vimentin, PCNA, p-AKT and p-mTOR expressions, while overexpression of HOXA1 had the opposite effects. Collectively, HOXA1 boosts migration, invasion and cell cycle, while suppressing cisplatin sensitivity of LC cells by mediating AKT/mTOR pathway, hinting that HOXA1 is a promising biomarker for diagnosis and prognosis of LC in clinical practice.
研究领域:
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2021
·Vol. 13
·期 17
·2929
·
IF 4.329
Jing Miao,Liwen Zhang,Peng Gao,Huawei Zhao,Xianji Xie,Junyan Wang
Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector LipofectamineTM2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.Keywords:GLUT-1;siRNA;chitosan oligosaccharide grafted stearic acid;laryngocarcinoma;radiosensitization
研究领域:
癌症生物学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL PAPERS
·
2022
·Vol. 76
·期 5
·2875-2882
·
IF 2.146
He Xiao-Ling,Huang Fu-Hui,Zhang Chun-Ming,Dong Zhen,Wang Bin-Quan
The larynx is an important organ of human speech, and patients with laryngeal cancer may face great pain of losing their functions. For the prevention and therapy of laryngeal carcinoma, two new Zn(II)/Cd(II) coordination polymers, namely [Zn 3 (L) 2 (4,4′-bipy)] n ·2n(DMF) ( 1 ) and [Cd 3 (L) 2 (bpp 2 ) n ·2n(H 2 O)·2n(DMF) ( 2 ) (H 3 L = 4,4′,4′′-ticarboxytriphenylamine, 4,4′-bipy = 4,4′-bipyridine, bpp = 1,3-bis(4-pyridyl)propane, DMF = N,N-dimethylformamide), were prepared. The treatment and protection activity of the new compounds against the laryngeal carcinoma was evaluated in this research, and the corresponding mechanism was explored at the same time. Firstly, CCK-8 assay was conducted to measure the inhibitory activity of compounds on the viability of laryngeal carcinoma cells. Additionally, the expression of miR-223-3P in MSC exosomes was also measured by real time RT-PCR assay.
研究领域:
肿瘤学
·
药理学
·
生物化学
✓ 已验证
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2014
·Vol. 38
·期 10
·4830-4836
·
IF 3.159
Xueshibojie Liu,Dan Yu,Chunshun Jin,Xiaowei Song,Jinzhang Cheng,Xue Zhao,Xinmeng Qi,Guangxin Zhang
We report a dual-responsive targeted drug delivery system (DDS) based on smart polymer coated mesoporous silica for laryngeal carcinoma therapy. Thermo/pH-coupling sensitive polymer poly[(N-isopropylacrylamide)-co-(methacrylic acid)] was grafted onto mesoporous silica active as a “valve” to moderate the diffusion of the embedded drugs in and out of the pore channels. The DDS showed a low level of drug leakage at low temperature/high pH values, but the significantly enhanced release at higher temperature/lower pH values, which exhibits an apparent thermo/pH controlled “on–off” drug release pattern. Most importantly, covalent binding of folic acid molecules to the composite allowed it to specifically target Hep2 cells, laryngeal squamous cancer cells with folic acid receptors. These results demonstrated that the composite nanoparticles were thermo/pH-coupling sensitive responsive, implying that the designed biocompatible system could be potentially applied as target release drug nanocarriers for laryngeal carcinoma therapy.
研究领域:
生物材料学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
npj Precision Oncology
·
2025
·Vol. 9
·期 1
·1-21
·
IF 8
Li Xiaoli,Wang Jiashuo,Guo Jiaxing,Zhang Ming
Cisplatin resistance is a major challenge in laryngeal cancer treatment. Tumor necrosis factor-alpha-induced protein 2 (TNFAIP2) has been implicated in chemoresistance, though its role in laryngeal cancer remains unclear. We identified TNFAIP2 as a key gene associated with cisplatin resistance and developed a second near-infrared (NIR-II) light-responsive CRISPR-Cas9 nanosystem (APC@RBCs) to target it. In cisplatin-resistant Tu177/CDDP cells, light-activated knockout of TNFAIP2 significantly increased cisplatin sensitivity (IC50 reduced from 12.55 to 4.37 µg/mL). Mechanistic studies revealed that TNFAIP2 modulates cisplatin resistance via the NRF2 pathway, affecting oxidative stress response and epithelial-mesenchymal transition. TNFAIP2 deletion also suppressed cancer cell migration and invasion. Our results establish TNFAIP2 as a critical mediator of chemoresistance and demonstrate the potential of APC@RBCs as a precise, non-invasive gene therapy platform. This strategy offers a promising approach to overcoming cisplatin resistance and improving treatment outcomes in laryngeal cancer patients.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
纳米技术
·
基因工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
·
2020
·Vol. 42
·期 9
·2287-2297
·
IF 2.538
Li-Bo Dai,Qi Yu,Shui-Hong Zhou,Yang-Yang Bao,Jiang-Tao Zhong,Li-Fang Shen,Zhong-Jie Lu,Jun Fan,Ya-Ping Huang
Background This study is to explore the role of curcumin and GLUT-1 antisense oligodeoxynucleotides (AS-ODN) on autophagy modulation-initiated radiosensitivity. Methods BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy- and apoptosis-related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining. Results Combinations of curcumin and GLUT-1 AS-ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3-MA also had a promotion effect on irradiation-mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT-1 AS-ODN-mediated growth inhibition potentially by regulating autophagic events. Of note, a de-escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT-1 AS-ODN or 3-MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone. Conclusions Curcumin and GLUT-1 AS-ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.
研究领域:
肿瘤学
·
药理学
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FLUORESCENCE
·
2024
·
IF 2.6
Zhu Hongmei,Yang Bo,Niu Yang,Huang Yongjiu
Laryngeal cancer, a common malignant respiratory tumor, is primarily treated through surgery. However, challenges such as recurrence, metastasis, and drug resistance persist. In recent years, multifunctional drug delivery systems (DDS) based on nanoparticles have shown great potential in improving drug loading and release. We developed a biocompatible core-shell nanoparticle system with a zinc-based metal-organic framework (MOF) as the core, named CP1. The shell, composed of polyethyleneimine (PEI), folic acid, and calcium carbonate, forms a composite called CaCO 3 -PEI-FA. This system enhances biocompatibility and increases the efficacy of biomedical applications. Encapsulating CP1 within the CaCO 3 -PEI-FA shell allows for the targeted delivery of the anticancer drug doxorubicin (DOX) to laryngeal cancer cells (Hep-2), resulting in the CaCO 3 -PEI-FA@CP1@DOX system. The CaCO 3 -PEI-FA composite exhibits strong fluorescence with a peak around 350 nm, confirming successful synthesis and demonstrating its potential as a bioimaging probe. Importantly, the nanoparticle system without DOX showed low toxicity to normal human skin fibroblasts (HSF). In vitro cytology experiments revealed a 38% inhibition rate of Hep-2 cells after 24 h, highlighting the nanocomposite’s significant potential in inhibiting laryngeal cancer cell proliferation and inducing apoptosis, underscoring its promise in targeted laryngeal cancer therapy.
研究领域:
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Xiaoyan Xu,Tianhao Zhou,Xudong Wei,Xuelian Jiang,Jiyan Cao
Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.
研究领域:
肿瘤学
·
纳米技术
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Jinghua Sun,Liping Li,Wenwen Cai,Anqi Chen,Ruiping Zhang
Laryngeal cancer is highly aggressive and insensitive to conventional targeted therapies, which often result in poor therapeutic outcomes. Image-guided precision therapy is a promising strategy in oncology that has superior safety and efficacy versus conventional therapies. Here, we present a multifunctional theranostic nanoplatform based on melanin-coated gold nanorod (GNR) that exhibits excellent multimodal imaging ability and photothermal effects. These attributes make the platform applicable for multimodal photoacoustic (PA)/positron emission tomography (PET)/magnetic resonance (MR) image-guided photothermal treatment of laryngeal cancer. The melanin nanoparticles markedly suppress the cytotoxicity of the template cetyltrimethylammonium bromide bilayer and conferred the GNR with excellent PET/MR imaging performances, due to their native biocompatibilities and strong affinities to metal ions. Moreover, the introduction of GNR to the melanin nanoparticles greatly improved the near-infrared absorbances and passive targeting capabilities, leading to exceptional PA imaging and photothermal ablation of tumors. The nanoplatform exhibits high stability and dispersity under physiological conditions. After intravenous injection, the nanoplatform could be precisely tracked in vivo and enabled laryngopharyngeal superficial cancer to be located and imaged. Combined photothermal therapy effectively ablated tumors with negligible side effects. Thus, this work presents a unique and biocompatible nanoplatform that allows multimodal imaging, high anti-tumor PTT efficacy, and negligible side effects in the treatment of laryngeal cancer.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
·
成像科学
✓ 已验证
产品关联
DOI
PubMed
危险品化学品经营许可证（带存储）