vernodalin 通过抑制 FAK/PI3K/AKT/mTOR 和 MAPKs 信号通路抑制胃癌细胞增殖并增加细胞凋亡。
Vernodalin Suppresses Tumor Proliferation and Increases Apoptosis of Gastric Cancer Cells Through Attenuation of FAK/PI3K/AKT/mTOR and MAPKs Signaling Pathways.
机构信息
Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Cancer Center, Zhejiang University, Hangzhou, 310058, China.
出版信息
Curr Pharm Biotechnol. 2023;24(5):708-717. doi: 10.2174/1389201023666220728150544.
BACKGROUND
Gastric cancer (GC) is the most aggressive malignant tumor with limited treatment alternatives post metastasis. Vernodalin (VN) induced apoptosis has been reported in various types of human cancer cells. However, the precise molecular mechanisms underlying the anti-metastasis action of VN on GC cells are yet to be elucidated.
OBJECTIVE
In this study, we investigated the anti-metastatic and apoptotic effects of VN on SGC- 7901 and AGS cells, with a purpose of gaining a deeper understanding of the anti-metastatic mechanisms of VN on gastric carcinoma. To attenuate the activation of PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by VN in GC cells.
METHODS
We employed VN and gastric cancer cells in experiments such as MTT assay, apoptosis, MMP, DAPI, Rh-123, cell adhesion assay, and western blot analysis on GC SGC-7901 and AGS cells.
RESULTS
Our results revealed that VN inhibits cell proliferation, adhesion, and metastasis and induces apoptosis of both GC cells. VN potentially reduced the protein expressions of MMP-2, MMP-9, and uPA, whereas intensified expressions of TIMP-1 and TIMP-2. Also, VN attenuates the expression of FAK, p-PI3K, p-AKT, p-mTOR, p-JNK, p-p38MAPK, and p-ERK. Thus, it is inferred that VN treatment reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/ mTOR, and MAPKs signaling pathways. Our results confirm that VN prevented GC growth, invasion and metastasis and induce apoptosis in GC cells.
CONCLUSION
Our findings suggest that VN is a potential natural therapeutic compound as a new remedy for GC chemotherapy treatment.
背景
胃癌（GC）是一种侵袭性最强的恶性肿瘤，转移后治疗选择有限。已经报道 Vernodalin（VN）在各种类型的人类癌细胞中诱导细胞凋亡。然而，VN 对 GC 细胞抗转移作用的确切分子机制仍有待阐明。
目的
本研究旨在探讨 VN 对 SGC-7901 和 AGS 细胞的抗转移和凋亡作用，以期深入了解 VN 对胃癌的抗转移机制。以减轻 VN 在 GC 细胞中对 PI3K/AKT/mTOR 和丝裂原活化蛋白激酶（MAPK）信号通路的激活。
方法
我们在 GC SGC-7901 和 AGS 细胞中进行了 VN 和胃癌细胞的实验，如 MTT 测定、凋亡、MMP、DAPI、Rh-123、细胞黏附测定和 Western blot 分析。
结果
我们的结果表明，VN 抑制 GC 细胞的增殖、黏附和转移，并诱导细胞凋亡。VN 可能降低 MMP-2、MMP-9 和 uPA 的蛋白表达，同时增强 TIMP-1 和 TIMP-2 的表达。此外，VN 减弱了 FAK、p-PI3K、p-AKT、p-mTOR、p-JNK、p-p38MAPK 和 p-ERK 的表达。因此，可以推断 VN 通过 FAK/PI3K/AKT/mTOR 和 MAPKs 信号通路降低了 MMP-2 和 MMP-9 的活性。我们的结果证实，VN 可预防 GC 生长、侵袭和转移，并诱导 GC 细胞凋亡。
结论
我们的研究结果表明，VN 是一种潜在的天然治疗化合物，可作为 GC 化疗治疗的新方法。
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