The Effect of Fuzheng Yiai Decoction on the Transdifferentiation of Lung Adenocarcinoma in EGFR-TKI-Resistant Mice.

Abstract

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.