CARCINOGENESIS
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2024
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IF 3.3
Yang Xin,Cui Limei,Liu Zhonglu,Li Yumei,Wu Xinxin,Tian Ruxian,Jia Chuanliang,Ren Chao,Mou Yakui,Song Xicheng
Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell, and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy, and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared to normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion, and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.
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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病理学
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产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2018
·Vol. 50
·期 6
·567-578
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IF 2.224
Zhang Yingying,Cong Linhai,He Jiayan,Wang Yu,Zou Yingying,Yang Zhihong,Hu Yuexin,Zhang Shiwen,He Xiaoguang
Hypopharyngeal carcinoma (HC) is one of the most malignant tumors in the upper aerodigestive tract. Currently, there are no effective treatments for HC. Gold nanoparticles (AuNPs) are a promising tool that can be used for plasmonic photothermal therapy (PPTT), which refers to the use of electromagnetic radiation, most often in near infrared (NIR) region, for the treatment of various medical conditions including cancer. AuNPs have been proved to be a promising tool for NIR spectroscopy-mediated photothermal therapies. In this study, we chemically conjugated AuNPs with a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR), a cell-surface receptor that is overexpressed in many cancers. We then assessed the effect of NIR photothermal treatment with the EGFRmAb–AuNPs in FaDu HC cells. Our data showed that nanoparticle conjugation with the EGFRmAb improved the specific targeting towards FaDu cells and reduced cytotoxicity towards normal (293 T) cells which do not overexpress the EGFR. A significant amount of our EGFRmAb-conjugated AuNPs could enter the nucleus. Moreover, the expression levels of double strand DNA break repair proteins, including p-ATR, p-CHK1, and p-CHK2 were increased following AuNPs treatment, indicating the presence of DNA damage. These findings suggest that the AuNPs can potentially disrupt genome integrity and induce apoptosis. In addition, EGFRmAb–AuNPs+NIR could induce FaDu cell apoptosis, accompanied by the inhibition of the PI3K/AKT/mTOR pathway and stimulation of DNA damage response. Based on these data, PPTT using the EGFRmAb–AuNPs could be a new promising treatment for HC.
研究领域:
肿瘤学
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纳米技术
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
CANCER CHEMOTHERAPY AND PHARMACOLOGY
·
2023
·Vol. 92
·期 3
·211-221
·
IF 3
Wang Dongbo,Wu Huina,Wu Qian,Liu Qi,Li Yamei,Wu Jiyong,Nie Jing
Purpose Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer. In recent years, the modification of platinum(II) into platinum(IV) derivative compounds, by introducing biologically active molecules, has been extensively employed to develop novel platinum-based prodrugs. We investigated the anti-proliferative activity against HNSCC of a new veratric acid (COX-2 inhibitor)-platinum(IV) complex. Methods In this study, a new veratric acid (COX-2 inhibitor)–platinum(IV) complex, termed veratricplatin, was synthesized. We evaluated the anti-tumor effect of in vitro and in vivo by western blotting, flow cytometry and DNA damage analysis. Results Veratricplatin displayed remarkable anti-proliferative activity against various cancer cell lines, including A549, FaDu, HeLa, and MCF-7. Furthermore, veratricplatin demonstrated significantly stronger cytotoxicity than either platinum(II) or veratric acid monotherapy or their combination. Importantly, the synthesized prodrug exhibited less toxicity toward normal cells (MRC-5), while dramatically enhanced DNA damage in FaDu cells inducing apoptosis. Moreover, veratricplatin markedly reduced the migration ability of FaDu cells compared to the control or monotherapy. In vivo, veratricplatin displayed potent anti-tumor activity with no apparent toxicity in BALB/c nude mice bearing FaDu tumors. In addition, tissue immunofluorescence analysis revealed that veratricplatin could substantially inhibit the formation of tumor blood vessels. Conclusion Veratricplatin demonstrated remarkable drug efficacy, in terms of increased cytotoxicity in vitro and high efficiency with low toxicity in vivo.
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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癌症研究
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产品关联
DOI
PubMed
高影响因子
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