Sun Jianfeng, Luo Danqing, Li Hui, Zhang Di, Liu Yesha, Jin Song, Guo Hong, He Chengshi, Wu Zhipeng
Department of Rehabilitation, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
Sichuan Acupuncture and Moxibustion School, Chengdu 610097, China.
Can Respir J. 2024 Dec 19;2024:8827810. doi: 10.1155/carj/8827810. eCollection 2024.
This study aimed to investigate the effect of Fuzheng Yiai Decoction (FZYA) on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) drug resistance in lung adenosquamous carcinoma (ASC). The expression of thyroid transcription factor 1 (TTF1) and p63 in tumor cells was observed by immunofluorescence staining. Meanwhile, 25 nude mice successfully inoculated with the human lung ASC cell line NCI-H596 were randomly divided into five groups, namely, the model, gefitinib, low-, medium-, and high-dose FZYA with gefitinib groups. After four weeks of daily intragastric administration of the various treatments, the tumor weight and volume inhibition rates were calculated. The positive expression rate and protein expression of TTF1 and p63 in mouse tumor tissues were evaluated by immunohistochemistry and western blot assays. The results showed that the adenocarcinoma part and the squamous cell carcinoma part of the lung tissue were not either one or the other, and each had unique biological behavior patterns. In terms of the tumor volume and weight, gefitinib treatment along with FZYA reduced the acquired resistance of EGFR-TKIs in lung ASC, and its inhibitory effect was superior to EGFR-TKI (gefitinib) treatment alone. Moreover, it was discovered that FZYA inhibited the pedigree transformation among cancer subtypes due to EGFR-TKI treatment. In conclusion, the application of FZYA inhibited the pedigree transformation among lung cancer subtypes, thus increasing the tumor inhibitory effect and decreasing the EGFR-TKI drug resistance of tumor cells.
本研究旨在探讨扶正抑癌汤（FZYA）对肺腺鳞癌（ASC）中表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）耐药性的影响。通过免疫荧光染色观察肿瘤细胞中甲状腺转录因子1（TTF1）和p63的表达。同时，将25只成功接种人肺ASC细胞系NCI-H596的裸鼠随机分为五组，即模型组、吉非替尼组、低、中、高剂量FZYA联合吉非替尼组。每日灌胃给予各种处理四周后，计算肿瘤重量和体积抑制率。通过免疫组织化学和蛋白质印迹分析评估小鼠肿瘤组织中TTF1和p63的阳性表达率和蛋白表达。结果表明，肺组织的腺癌部分和鳞癌部分并非单纯的某一种，各自具有独特的生物学行为模式。在肿瘤体积和重量方面，吉非替尼与FZYA联合治疗降低了肺ASC中EGFR-TKIs的获得性耐药性，其抑制作用优于单纯EGFR-TKI（吉非替尼）治疗。此外，发现FZYA抑制了因EGFR-TKI治疗导致的癌症亚型间的谱系转化。总之，FZYA的应用抑制了肺癌亚型间的谱系转化，从而增强了肿瘤抑制作用并降低了肿瘤细胞的EGFR-TKI耐药性。
