黄连解毒汤调控自噬治疗皮肤鳞状细胞癌的机制研究OACHSSCD

Objective:To investigate the effects of Huanglian Jiedu Decoction on autophagy levels in a mouse model of cutaneous squamous cell carcinoma(cSCC)and its regulatory effects on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway.Methods:Male mice were randomly divided into a blank group,a mod-el group,and high-,medium-,and low-dose Huanglian Jiedu Decoction groups(HLJD-H,HLJD-M,HLJD-L).Except for the blank group,the cSCC model was established in all groups using the 7,12-dimethylbenz[a]anthracene(DMBA)/12-O-tetradecanoylphor-bol-13-acetate(TPA)chemical induction method.Hematoxylin-eosin(HE)staining was used to observe the morphological structure of skin tissues.Immunohistochemistry was performed to detect epidermal growth factor receptor(EGFR)expression.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α).Quantitative polymerase chain reaction(qPCR)was used to detect the mRNA expression of autophagy-related genes,including Beclin1,microtubule-associated protein 1 light chain 3 Ⅱ(LC3 Ⅱ),and autophagy-related gene 5(Atg5).Western blot analysis was used to determine the protein expression levels of PI3K,AKT,and mTOR.Results:Compared with the blank group,the model group showed marked proliferation of skin tumor cells accompanied by inflammatory cell infiltration,with increased expression of EGFR,IL-6,IL-1β,TNF-α,PI3K,AKT,and mTOR(all P＜0.01),and significantly decreased mRNA expression of Beclin1,LC3 Ⅱ,and Atg5(all P＜0.01).Compared with the model group,the HLJD groups showed significant improvement in tumor cell proliferation and inflammatory cell infiltration,decreased expression of EGFR,IL-6,IL-1β,TNF-α,PI3K,AKT,and mTOR(all P＜0.05),and significantly increased mRNA expression of Beclin1,LC3 Ⅱ,and Atg5(all P＜0.05).Conclusion:Huanglian Jiedu Decoction can enhance autophagy in cSCC model mice,inhibit tumor growth and inflammatory mediator expres-sion,thereby exerting therapeutic effects.The underlying mechanism may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.