School of Public Health, Kunming Medical University, Kunming, Yunnan Province, 650500, China.
Institute of Yunnan Tumor, the Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650118, China.
Curr Cancer Drug Targets. 2023;23(7):572-584. doi: 10.2174/1568009623666230227162532.
HMOX1 has a dual role in cancers, especially involving chemoresistance. We demonstrate that cephalosporin antibiotics exert strong anticancer activity in nasopharyngeal carcinoma mainly via drastic upregulation of HMOX1.
Cephalosporin antibiotics are commonly used for the treatment or prophylaxis of bacterial infectious diseases in cancer patients. It is unknown whether they lead to chemoresistance in cancer patients, especially in nasopharyngeal carcinoma patients, who are being treated or required prophylaxis for an infectious syndrome with cephalosporin antibiotics.
MTT and clonogenic colony formation assays assessed the viability and proliferation of cultured cancer cells. Flow cytometry was used to detect apoptosis. Tumor growth was assessed using a xenograft model. Microarray and RT-qPCR expression analyses investigated differential gene expression.
Cefotaxime enhanced anticancer efficacy of cisplatin in nasopharyngeal carcinoma without enhancing the toxic side effects both and . However, cefotaxime significantly reduced the cytotoxicity of cisplatin in other cancer cell lines. Cefotaxime and cisplatin co-regulated 5 differential genes in CNE2 cells in a direction supporting the enhancement of anticancer efficacy, of which, THBS1 and LAPTM5 were further upregulated, STAG1, NCOA5, and PPP3CB were further downregulated. Out of the 18 apoptotic pathways significantly enriched in the combination group, THBS1 and HMOX1 overlapped in 14 and 12 pathways, respectively. Extrinsic apoptotic signaling pathway (GO: 2001236) was the only apoptotic pathway commonly enriched in cefotaxime group, cisplatin group and combination group, and THBS1 and HMOX1 were the overlapped genes of this pathway. THBS1 also overlapped in P53 signaling pathway and ECM-receptor interaction signaling pathway enriched by KEGG.
Cephalosporin antibiotics are chemosensitizers of conventional chemotherapeutic drugs in the chemotherapy of nasopharyngeal carcinoma, but they may lead to chemoresistance by cytoprotection in other cancers. Cefotaxime and cisplatin co-regulate THBS1, LAPTM5, STAG1, NCOA5 and PPP3CB suggesting their involvement in the enhancement of anticancer efficacy in nasopharyngeal carcinoma. Targeting of P53 signaling pathway and ECM-receptor interaction signaling pathway was correlated to the enhancement. With additional benefit for treatment or prophylaxis of an infectious syndrome, cephalosporin antibiotics can benefit the therapy of nasopharyngeal carcinoma either as anticancer agents or as chemosensitizers of chemotherapeutic drugs in combination chemotherapy.
HMOX1 在癌症中具有双重作用，特别是涉及化学耐药性。我们证明头孢菌素抗生素通过剧烈上调 HMOX1 在鼻咽癌中具有很强的抗癌活性。
头孢菌素抗生素通常用于治疗或预防癌症患者的细菌感染性疾病。目前尚不清楚它们是否会导致癌症患者，特别是正在接受头孢菌素抗生素治疗或需要预防感染综合征的鼻咽癌患者产生化学耐药性。
MTT 和集落形成实验评估培养的癌细胞的活力和增殖。流式细胞术用于检测细胞凋亡。异种移植模型用于评估肿瘤生长。微阵列和 RT-qPCR 表达分析研究差异基因表达。
头孢噻肟在不增强毒性副作用的情况下增强了鼻咽癌中顺铂的抗癌疗效。然而，头孢噻肟显着降低了其他癌细胞系中顺铂的细胞毒性。头孢噻肟和顺铂共同调节 CNE2 细胞中的 5 个差异基因，方向支持抗癌疗效的增强，其中 THBS1 和 LAPTM5 进一步上调，STAG1、NCOA5 和 PPP3CB 进一步下调。在组合组中显着富集的 18 个凋亡途径中，THBS1 和 HMOX1 分别在 14 和 12 条途径中重叠。外源性凋亡信号通路（GO：2001236）是唯一在头孢噻肟组、顺铂组和联合组中共同富集的凋亡通路，THBS1 和 HMOX1 是该通路的重叠基因。THBS1 还与 KEGG 中富集的 P53 信号通路和 ECM-受体相互作用信号通路重叠。
头孢菌素抗生素是鼻咽癌化疗中常规化疗药物的化疗增敏剂，但在其他癌症中可能通过细胞保护作用导致化学耐药性。头孢噻肟和顺铂共同调节 THBS1、LAPTM5、STAG1、NCOA5 和 PPP3CB，表明它们参与了鼻咽癌抗癌疗效的增强。针对 P53 信号通路和 ECM-受体相互作用信号通路的靶向治疗与增强作用相关。由于具有治疗或预防感染综合征的额外益处，头孢菌素抗生素可以作为抗癌药物或作为联合化疗中化疗药物的化疗增敏剂，有益于鼻咽癌的治疗。
