姜黄素逆转HGF诱导PC9细胞对吉非替尼的耐药

目的:探索姜黄素逆转肝细胞生长因子(HGF)诱导的肺癌细胞吉非替尼耐药性的分子机制。方法:利用MTT实验、划痕修复实验和Western blot观察HGF、吉非替尼和姜黄素对PC9细胞药物敏感性、迁移能力、上皮间质转化和相关信号通路的影响.结果:HGF可显著降低PC9细胞对吉非替尼的敏感性,而姜黄素可显著逆转HGF诱导的PC9细胞对吉非替尼的耐药性。HGF还可诱导PC9细胞发生迁移及上皮间质转化,激活c-Met/AKT/mTOR通路,单独吉非替尼不能逆转HGF诱导的迁移、上皮间质转化及c-Met/AKT/mTOR通路活化,而吉非替尼联合姜黄素可抑制HGF诱导的c-Met/AKT/mTOR通路活化并逆转PC9细胞的迁移和上皮间质转化。结论:姜黄素抑制HGF诱导的PC9细胞吉非替尼耐药性可能是通过逆转上皮间质转化和抑制c-Met/AKT/mTOR通路实现的。

Curcumin reverses hepatocyte growth factor-induced resistance to gefitinib in PC9 lung cancer cells

AIM: To explore the molecular mechanism through which curcumin reverses hepatocyte growth factor (HGF)-induced resistance to gefitinib in lung cancer cells.METHODS: The methods of MTT assay, wound healing assay and Western blot were used to observe the effects of HGF, curcumin and gefitinib on the migration, drug susceptibility, epithelial-mesenchymal transition, and related signaling pathways in the PC9 lung cancer cells.RESULTS: HGF reduced susceptibility of the PC9 cells to gefitinib, and curcumin significantly reversed HGF-induced resistance to gefitinib. HGF induced migration and epihelial-mesenchymal transition, and promoted c-Met/AKT/mTOR pathway activation in the PC9 cells. Gefitinib alone did not prevent the above activities. However, combined with curcumin, gefitinib prevented the above activities.CONCLUSION: Curcumin reverses HGF-induced resistance of the PC9 cells to gefitinib by preventing epithelial-mesenchymal transition and inhibiting c-Met/AKT/mTOR activation.