科研之友
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摘要
As the first-line drug therapy for non-small cell lung cancer (NSCLC), cisplatin has a wide range of applications. However, inherent and acquired resistance reduces its effectiveness in the treatment of NSCLC. Our study was to investigate the antitumor activity of a new camptothecin analogue FL118 on cisplatin-resistant NSCLC cells. Western blot assay showed that the expression of survivin protein down-regulated by FL118, Flow cytometry analysis displayed that A549 cells and its cisplatin-resistant counterparts (A549/DDP) cells were both arrested in S phase. MTT assay showed that the viability of A549/DDP cells were decreased, indicating that FL118 may effectively inhibit the growth of NSCLC cells regardless of the chemoresistance of tumor cells. Meanwhile, wound healing scratch assay and transwell-matrigel invasion assay were used to demonstrate that FL118 may inhibit the migratory and invasive capabilities of A549 and A549/DDP cells. To further explore the mechanism of antitumor activity of FL118, the expression of ERCC1, P-gp, E-cadherin and Vimentin proteins were examined by immunohistochemistry and western blot. The resistance-associated proteins, P-gp and ERCC1, were both inhibited by the treatment of FL118, suggesting that FL118 may promote the chemosensitivity of tumor cells through inhibiting their expression. Consistent with the change in chemosensitivity, epithelial-mesenchymal transition (EMT) of A549/DDP cells was reversed by FL118, implying that the antitumor efficacy of FL118 is at least partly, dependent on regulating the process of EMT. These findings contribute to the the understanding of the molecular mechanism by which FL118 reverses cisplatin-resistance of NSCLC cells and demonstrates that FL118 is a promising candidate for further clinical lung cancer treatment.
- 出版日期2016
- 单位青岛大学
