Article(id=1304414714939859451, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304414700964443026, articleNumber=null, orderNo=null, doi=10.7501/j.issn.0253-2670.2026.04.012, pmid=null, cstr=null, oa=null, hot=0, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1762704000000, receivedDateStr=2025-11-10, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1788926302895, onlineDateStr=2026-09-09, pubDate=null, pubDateStr=null, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1788926302895, onlineIssueDateStr=2026-09-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1788926302895, creator=13701087609, updateTime=1788926302895, updator=13701087609, issue=Issue{id=1304414700964443026, tenantId=1146029695717560320, journalId=1302319053441957962, year='2026', volume='57', issue='4', pageStart='1209', pageEnd='1596', issueExtLink='null', onlineDate='null', pubDate='1772208000000', pubDateStr='2026-02-28', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1788926299563, creator='13701087609', updateTime=1788926573099, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1304415848316297970, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304414700964443026, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1304415848316297971, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304414700964443026, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1325, endPage=1335, ext={EN=ArticleExt(id=1304414716957319677, articleId=1304414714939859451, tenantId=1146029695717560320, journalId=1302319053441957962, language=EN, title=Effect and mechanism of bufotalin on growth of human head and neck squamous cell carcinoma, columnId=null, journalTitle=Chinese Traditional and Herbal Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=Objective To investigate the effect and potential mechanism of bufotalin on growth of human head and neck squamous cell carcinoma (HNSCC). Methods The effect of bufotalin on viability and proliferation of Cal-27 and FaDu cells were observed by CCK-8 method and plate clone formation experiment. The effect of bufotalin on cell cycle distribution of Cal-27 and FaDu cells were detected by flow cytometry. Western blotting was used to detect the effect of bufotalin on expressions of cyclin-dependent kinase 4 (CDK4) and cyclin D1 in Cal-27 and FaDu cells. To further explore the anti-tumor effects of bufotalin in vivo , a xenograft tumor model of HNSCC was established in nude mice. Proteomics technology was applied to identify differentially expressed proteins in bufotalin-treated Cal-27 cells, and the associated signaling pathways underlying its anti-tumor effect were analyzed. Western blotting was performed to assess the expressions of protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) signaling pathway related proteins. Results In vitro experimental results showed that bufotalin significantly reduced the viability of Cal-27 and FaDu cells (P < 0.01, 0.001), inhibited their proliferation (P < 0.01, 0.001), induced cell cycle arrest in G0 /G1 phase (P < 0.05, 0.01, 0.001), down-regulated the protein expressions of CDK4 and cyclin D1 in FaDu cells (P < 0.05, 0.001), and down-regulated the protein expression of CDK4 in Cal-27 cells (P < 0.05). The in vivo experimental results showed that bufotalin could significantly inhibit the growth of tumors in tumor bearing mice (P < 0.01, 0.001). Proteomics and IPA analysis showed that bufotalin could induce endoplasmic reticulum stress and up-regulate the expression levels of p-PERK and p-eIF2α in Cal-27 and FaDu cells (P < 0.05, 0.001). Conclusion Bufotalin could induce endoplasmic reticulum stress, activate EIF2 signaling pathway, and induce the arrest of HNSCC cells in G0 /G1 phase, thereby inhibiting tumor cell proliferation and tumor growth in tumor-bearing mice., authors=AN Xuejing, CUI Qixiao, ZHAO Ying, HE Xiaojuan, PAN Zhaohai, LI Defang, WANG Yuliang, ZHENG Qiusheng, authorsList=AN Xuejing, CUI Qixiao, ZHAO Ying, HE Xiaojuan, PAN Zhaohai, LI Defang, WANG Yuliang, ZHENG Qiusheng, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1304414715250237948, articleId=1304414714939859451, tenantId=1146029695717560320, journalId=1302319053441957962, language=CN, title=蟾蜍它灵对人头颈部鳞状细胞癌的影响及作用机制, columnId=1304140191707456168, journalTitle=中草药, columnName=药理与临床, runingTitle=null, highlight=null, articleAbstract=目的 探讨蟾蜍它灵对人头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）的影响及其潜在的作用机制。方法 采用CCK-8法和克隆形成实验，考察蟾蜍它灵对人舌鳞癌Cal-27细胞和人咽鳞癌FaDu细胞活力及增殖的影响；采用流式细胞术检测蟾蜍它灵对Cal-27和FaDu细胞周期分布的影响；采用Western blotting检测蟾蜍它灵对Cal-27和FaDu细胞内细胞周期蛋白依赖性激酶4（cyclin-dependent kinase 4，CDK4）和细胞周期蛋白D1（cyclin D1）表达的影响。构建裸鼠异种移植瘤模型，进一步验证蟾蜍它灵的体内抗肿瘤作用。通过蛋白质组学检测经蟾蜍它灵处理后的Cal-27细胞内差异表达的蛋白，并分析其发挥抗肿瘤作用的信号通路；采用Western blotting检测蛋白激酶R样内质网激酶（protein kinase R-like endoplasmic reticulum kinase，PERK）/真核翻译起始因子2α亚基（eukaryotic initiation factor 2α，eIF2α）信号通路相关蛋白的表达。结果 体外实验结果显示，蟾蜍它灵可显著降低Cal-27和FaDu细胞的活力（P ＜0.01、0.001），并抑制其增殖（P ＜0.01、0.001），诱导细胞周期阻滞于G₀/G₁期（P ＜0.05、0.01、0.001），下调FaDu细胞内CDK4和cyclin D1的蛋白表达（P ＜0.05、0.001），下调Cal-27细胞内CDK4蛋白表达（P ＜0.05）。体内实验结果显示，蟾蜍它灵可显著抑制荷瘤小鼠体内肿瘤的生长（P ＜0.01、0.001）。蛋白质组学和IPA分析表明蟾蜍它灵能引起内质网应激，上调Cal-27和FaDu细胞内p-PERK和p-eIF2α的表达水平（P ＜0.05、0.001）。结论 蟾蜍它灵可通过诱导内质网应激，激活EIF2信号通路，诱导HNSCC细胞阻滞于G₀/G₁期，进而抑制肿瘤细胞的增殖和荷瘤小鼠体内肿瘤的生长。, authors=安雪菁1 , 崔齐晓1 , 赵盈1 , 何小鹃2 , 潘钊海1 , 李德芳1 , 王玉良3,4 , 郑秋生1 , authorsList=安雪菁, 崔齐晓, 赵盈, 何小鹃, 潘钊海, 李德芳, 王玉良, 郑秋生, authorCompany=1 滨州医学院中医学院, 山东省高等学校 中药活性成分生物合成与靶点发现特色实验室, 山东烟台 264003; et al . Head and neck squamous cell carcinoma [J]. Nat Rev Dis Primers , 2020, 6(1): 92.et al . HNSCC: Tumour antigens and their targeting by immunotherapy [J]. Cells , 2020, 9(9): 2103.et al . Revolutionizing head and neck squamous cell carcinoma treatment with nanomedicine in the era of immunotherapy [J]. Front Immunol , 2024, 15: 1453753.et al . A comprehensive analysis into the therapeutic application of natural products as SIRT6 modulators in Alzheimer’s disease, aging, cancer, inflammation, and diabetes [J]. Int J Mol Sci , 2021, 22(8): 4180.et al . Bufotalin induces ferroptosis in non-small cell lung cancer cells by facilitating the ubiquitination and degradation of GPX4[J]. Free Radic Biol Med , 2022, 180: 75-84.Nat Rev Mol Cell Biol , 2022, 23(1): 74-88.2 /M-phase checkpoint in human cells [J]. Cell Cycle , 2020, 19(1): 84-96.Cell Death Differ , 2022, 29(5): 946-960.Methods Mol Biol , 2022, 2579: 3-23.et al . Targeting the PI3K/Akt/mTOR pathway in hepatocellular carcinoma [J]. Biomedicines , 2021, 9(11): 1639.et al . Isovalerylspiramycin I suppresses small cell lung cancer proliferation via ATR/CHK1 mediated DNA damage response and PERK/eIF2α/ATF4/CHOP mediated ER stress [J]. Biochem Pharmacol , 2024, 230(Pt 1): 116557.Trends Cell Biol , 2020, 30(8): 606-618.et al . The origins and evolution of translation factors [J]. Trends Genet , 2025, 41(7): 590-600.et al . Activation of the integrated stress response by inhibitors of its kinases [J]. Nat Commun , 2023, 14(1): 5535.et al . EGFR confers radioresistance in human oropharyngeal carcinoma by activating endoplasmic reticulum stress signaling PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78[J]. Cancer Med , 2018, 7(12): 6234-6246.et al . Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation [J]. Cell Commun Signal , 2025, 23(1): 164.et al . Inhibition of endoplasmic reticulum stress-mediated autophagy enhances the anticancer effect of iodine-125 seed radiation on esophageal squamous cell carcinoma [J]. Radiat Res , 2020, 194(3): 236-245.et al . Benzyl isothiocyanate induces protective autophagy in human lung cancer cells through an endoplasmic reticulum stress-mediated mechanism [J]. Acta Pharmacol Sin , 2017, 38(4): 539-550.Biomolecules , 2025, 15(2): 248.et al . Cancer drug resistance: An evolving paradigm [J]. Nat Rev Cancer , 2013, 13(10): 714-726.)
中草药
|药理与临床
2026
, 57
(4) :
1325
-1335
蟾蜍它灵对人头颈部鳞状细胞癌的影响及作用机制
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安雪菁1 , 崔齐晓1 , 赵盈1 , 何小鹃2 , 潘钊海1 , 李德芳1 , 王玉良3,4 , 郑秋生1
作者信息
1 滨州医学院中医学院, 山东省高等学校 中药活性成分生物合成与靶点发现特色实验室, 山东烟台 264003;
通讯作者:
王玉良
作者简介:
安雪菁: 安雪菁，硕士研究生，主要从事中西医结合防治肿瘤的临床与基础研究。E-mail:15053598093@163.com
Effect and mechanism of bufotalin on growth of human head and neck squamous cell carcinoma
AN Xuejing, CUI Qixiao, ZHAO Ying, HE Xiaojuan, PAN Zhaohai, LI Defang, WANG Yuliang, ZHENG Qiusheng
Affiliations
doi: 10.7501/j.issn.0253-2670.2026.04.012
文章导航
目的 探讨蟾蜍它灵对人头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）的影响及其潜在的作用机制。方法 采用CCK-8法和克隆形成实验，考察蟾蜍它灵对人舌鳞癌Cal-27细胞和人咽鳞癌FaDu细胞活力及增殖的影响；采用流式细胞术检测蟾蜍它灵对Cal-27和FaDu细胞周期分布的影响；采用Western blotting检测蟾蜍它灵对Cal-27和FaDu细胞内细胞周期蛋白依赖性激酶4（cyclin-dependent kinase 4，CDK4）和细胞周期蛋白D1（cyclin D1）表达的影响。构建裸鼠异种移植瘤模型，进一步验证蟾蜍它灵的体内抗肿瘤作用。通过蛋白质组学检测经蟾蜍它灵处理后的Cal-27细胞内差异表达的蛋白，并分析其发挥抗肿瘤作用的信号通路；采用Western blotting检测蛋白激酶R样内质网激酶（protein kinase R-like endoplasmic reticulum kinase，PERK）/真核翻译起始因子2α亚基（eukaryotic initiation factor 2α，eIF2α）信号通路相关蛋白的表达。结果 体外实验结果显示，蟾蜍它灵可显著降低Cal-27和FaDu细胞的活力（P ＜0.01、0.001），并抑制其增殖（P ＜0.01、0.001），诱导细胞周期阻滞于G₀/G₁期（P ＜0.05、0.01、0.001），下调FaDu细胞内CDK4和cyclin D1的蛋白表达（P ＜0.05、0.001），下调Cal-27细胞内CDK4蛋白表达（P ＜0.05）。体内实验结果显示，蟾蜍它灵可显著抑制荷瘤小鼠体内肿瘤的生长（P ＜0.01、0.001）。蛋白质组学和IPA分析表明蟾蜍它灵能引起内质网应激，上调Cal-27和FaDu细胞内p-PERK和p-eIF2α的表达水平（P ＜0.05、0.001）。结论 蟾蜍它灵可通过诱导内质网应激，激活EIF2信号通路，诱导HNSCC细胞阻滞于G₀/G₁期，进而抑制肿瘤细胞的增殖和荷瘤小鼠体内肿瘤的生长。
蟾蜍它灵
/
头颈部鳞状细胞癌
/
细胞增殖
/
周期阻滞
/
内质网应激
/
EIF2信号通路
Objective To investigate the effect and potential mechanism of bufotalin on growth of human head and neck squamous cell carcinoma (HNSCC). Methods The effect of bufotalin on viability and proliferation of Cal-27 and FaDu cells were observed by CCK-8 method and plate clone formation experiment. The effect of bufotalin on cell cycle distribution of Cal-27 and FaDu cells were detected by flow cytometry. Western blotting was used to detect the effect of bufotalin on expressions of cyclin-dependent kinase 4 (CDK4) and cyclin D1 in Cal-27 and FaDu cells. To further explore the anti-tumor effects of bufotalin in vivo , a xenograft tumor model of HNSCC was established in nude mice. Proteomics technology was applied to identify differentially expressed proteins in bufotalin-treated Cal-27 cells, and the associated signaling pathways underlying its anti-tumor effect were analyzed. Western blotting was performed to assess the expressions of protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) signaling pathway related proteins. Results In vitro experimental results showed that bufotalin significantly reduced the viability of Cal-27 and FaDu cells (P < 0.01, 0.001), inhibited their proliferation (P < 0.01, 0.001), induced cell cycle arrest in G0 /G1 phase (P < 0.05, 0.01, 0.001), down-regulated the protein expressions of CDK4 and cyclin D1 in FaDu cells (P < 0.05, 0.001), and down-regulated the protein expression of CDK4 in Cal-27 cells (P < 0.05). The in vivo experimental results showed that bufotalin could significantly inhibit the growth of tumors in tumor bearing mice (P < 0.01, 0.001). Proteomics and IPA analysis showed that bufotalin could induce endoplasmic reticulum stress and up-regulate the expression levels of p-PERK and p-eIF2α in Cal-27 and FaDu cells (P < 0.05, 0.001). Conclusion Bufotalin could induce endoplasmic reticulum stress, activate EIF2 signaling pathway, and induce the arrest of HNSCC cells in G0 /G1 phase, thereby inhibiting tumor cell proliferation and tumor growth in tumor-bearing mice.
bufotalin
/
head and neck squamous cell carcinoma
/
cell proliferation
/
cycle arrest
/
endoplasmic reticulum stress
/
EIF2 signaling pathway
安雪菁, 崔齐晓, 赵盈, 何小鹃, 潘钊海, 李德芳, 王玉良, 郑秋生.
蟾蜍它灵对人头颈部鳞状细胞癌的影响及作用机制.
中草药,
2026
, 57
(4)
: 1325
-1335
.
DOI: 10.7501/j.issn.0253-2670.2026.04.012
AN Xuejing, CUI Qixiao, ZHAO Ying, HE Xiaojuan, PAN Zhaohai, LI Defang, WANG Yuliang, ZHENG Qiusheng.
Effect and mechanism of bufotalin on growth of human head and neck squamous cell carcinoma[J].
Chinese Traditional and Herbal Drugs ,
2026
, 57
(4)
: 1325
-1335
.
DOI: 10.7501/j.issn.0253-2670.2026.04.012
参考文献
引证文献
Johnson D E, Burtness B, Leemans C R, et al . Head and neck squamous cell carcinoma [J]. Nat Rev Dis Primers , 2020, 6(1): 92.et al . HNSCC: Tumour antigens and their targeting by immunotherapy [J]. Cells , 2020, 9(9): 2103.et al . Revolutionizing head and neck squamous cell carcinoma treatment with nanomedicine in the era of immunotherapy [J]. Front Immunol , 2024, 15: 1453753.et al . A comprehensive analysis into the therapeutic application of natural products as SIRT6 modulators in Alzheimer’s disease, aging, cancer, inflammation, and diabetes [J]. Int J Mol Sci , 2021, 22(8): 4180.et al . Bufotalin induces ferroptosis in non-small cell lung cancer cells by facilitating the ubiquitination and degradation of GPX4[J]. Free Radic Biol Med , 2022, 180: 75-84.Nat Rev Mol Cell Biol , 2022, 23(1): 74-88.2 /M-phase checkpoint in human cells [J]. Cell Cycle , 2020, 19(1): 84-96.Cell Death Differ , 2022, 29(5): 946-960.Methods Mol Biol , 2022, 2579: 3-23.et al . Targeting the PI3K/Akt/mTOR pathway in hepatocellular carcinoma [J]. Biomedicines , 2021, 9(11): 1639.et al . Isovalerylspiramycin I suppresses small cell lung cancer proliferation via ATR/CHK1 mediated DNA damage response and PERK/eIF2α/ATF4/CHOP mediated ER stress [J]. Biochem Pharmacol , 2024, 230(Pt 1): 116557.Trends Cell Biol , 2020, 30(8): 606-618.et al . The origins and evolution of translation factors [J]. Trends Genet , 2025, 41(7): 590-600.et al . Activation of the integrated stress response by inhibitors of its kinases [J]. Nat Commun , 2023, 14(1): 5535.et al . EGFR confers radioresistance in human oropharyngeal carcinoma by activating endoplasmic reticulum stress signaling PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78[J]. Cancer Med , 2018, 7(12): 6234-6246.et al . Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation [J]. Cell Commun Signal , 2025, 23(1): 164.et al . Inhibition of endoplasmic reticulum stress-mediated autophagy enhances the anticancer effect of iodine-125 seed radiation on esophageal squamous cell carcinoma [J]. Radiat Res , 2020, 194(3): 236-245.et al . Benzyl isothiocyanate induces protective autophagy in human lung cancer cells through an endoplasmic reticulum stress-mediated mechanism [J]. Acta Pharmacol Sin , 2017, 38(4): 539-550.Biomolecules , 2025, 15(2): 248.et al . Cancer drug resistance: An evolving paradigm [J]. Nat Rev Cancer , 2013, 13(10): 714-726.
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doi: 10.7501/j.issn.0253-2670.2026.04.012
接收时间：2025-11-10
首发时间：2026-09-09
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2种不同金属材料的力学参数
科 属数 种数 占总种数比例 属 种数 占总种数比例 鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78 小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39 多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39 红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87 小菇属 Mycena 11 5.26 光柄菇属 Pluteus 5 2.39 红菇属 Russula 17 8.13 栓菌属 Trametes 5 2.39
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