OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and...OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.展开更多
基金supported by National Nature Science Foundation of China(U1303221)National Natural Science Foundation of China(81373439,81473234)Construction of Technique Plate for Evaluation of the Pharmacodynamics of New Drugs in Xinjiang from the Department of Science and Technology of Xinjiang Province(201233150)
文摘OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.
文摘头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)是头颈部肿瘤最为常见的一种类型,其治疗效果及患者的预后并不理想,随着抗表皮生长因子受体(epidermal growth factor receptor,EGFR)单抗和免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的广泛应用,HNSCC患者的生存期虽有所延长但仍存在较大的改善空间。近年来多项研究提示,抗EGFR单抗联合ICIs治疗可带来良好的效果及安全性,已获得美国国立综合癌症网络(National Comprehensive Cancer Network,NCCN)和中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)等发布的权威性指南推荐。然而,抗EGFR单抗联合ICIs治疗方案的应用仍处于早期探索阶段,如何在临床中规范使用仍存在诸多待解答的问题,包括其协同作用机制、在不同类型患者中的治疗价值及安全性等。CSCO头颈肿瘤专家委员会组织专家基于循证医学证据及临床实践探索,经过多轮讨论,最终形成《抗EGFR单抗联合免疫检查点抑制剂治疗头颈部鳞状细胞癌专家共识(2025年版)》,对抗EGFR单抗与ICIs联合治疗的作用机制、分层治疗、在特殊人群中的应用及安全性等方面提出指导建议。本共识已在国际实践指南注册与透明化平台(Practice guideline REgistration for transPAREncy,PREPARE)上注册,注册号为PREPARE-2025CN666。期望本共识能够为临床医师提供更为明确和实用的指导,进一步推动该联合方案在临床实践中的合理应用,为HNSCC患者提供更多的治疗选择。
