Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.
Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.
Drug Des Devel Ther. 2020 Jan 29;14:395-405. doi: 10.2147/DDDT.S222694. eCollection 2020.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and it accounts for more than 90% of oral cancer. Due to high mortality, limitations of traditional treatment and many complications, new treatment methods are urgently needed. This study aimed to look into the effect of new potential anti-tumor drug, genipin, on OSCC treatment.
In vitro, CCK-8, colony formation, and flow cytometry were used to detect the effect of genipin on SCC-9 and SCC-15 cell lines. Immunofluorescence, real-time PCR, and Western blotting were used to investigate its mechanism. Xenograft tumor model was used to explore the role of genipin in vivo.
We found that genipin suppressed cell growth and induced apoptosis in vitro. In addition, the expression of p62 was down-regulated while Beclin1 and LC3II were up-regulated in SCC-25 and SCC-9 cells. 3-methyladenine (3-MA) significantly decreased LC3 (LC3II) puncta, but genipin rescuect 3d this reduction. Furthermore, genipin also reduced the expression of p-PI3K, p-AKT, and p-mTOR. In vivo experiment showed that genipin significantly curbed the tumor size and weight. The positive expression of Ki67 protein and number of apoptotic cells were increased.
Conclusively, this study implicated that genipin suppresses cell proliferation and stimulated apoptosis, and is the first exploration showing that genipin induces OSCC cell autophagy via PI3K/AKT/mTOR pathway inhibition.
口腔鳞状细胞癌（OSCC）是头颈部常见的恶性肿瘤，占口腔癌的 90%以上。由于死亡率高、传统治疗方法的局限性和许多并发症，迫切需要新的治疗方法。本研究旨在探讨新型潜在抗肿瘤药物京尼平对 OSCC 治疗的作用。
体外采用 CCK-8、集落形成和流式细胞术检测京尼平对 SCC-9 和 SCC-15 细胞系的作用。免疫荧光、实时 PCR 和 Western blot 用于研究其机制。异种移植肿瘤模型用于体内探索京尼平的作用。
我们发现京尼平在体外抑制细胞生长并诱导细胞凋亡。此外，在 SCC-25 和 SCC-9 细胞中，p62 的表达下调，而 Beclin1 和 LC3II 的表达上调。3-甲基腺嘌呤（3-MA）显著减少 LC3（LC3II）斑点，但京尼平挽救了这种减少。此外，京尼平还降低了 p-PI3K、p-AKT 和 p-mTOR 的表达。体内实验表明，京尼平显著抑制肿瘤大小和重量。Ki67 蛋白的阳性表达和凋亡细胞数量增加。
综上所述，本研究表明京尼平抑制细胞增殖并刺激细胞凋亡，并且是首次表明京尼平通过抑制 PI3K/AKT/mTOR 通路诱导 OSCC 细胞自噬。
