Merck

Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy.

International journal of oncology (2018-08-15)
Yi-Han Chiu, Shih-Hsien Hsu, Hsiao-Wei Hsu, Kuo-Chin Huang, Wangta Liu, Chang-Yi Wu, Wei-Pang Huang, Jeff Yi-Fu Chen, Bing-Hung Chen, Chien-Chih Chiu
RESUMEN

Lung cancer is a prevalent disease and is one of the leading causes of mortality worldwide. Despite the development of various anticancer drugs, the prognosis of lung cancer is relatively poor. Metastasis of lung cancer, as well as chemoresistance, is associated with a high mortality rate for patients with lung cancer. Camptothecin (CPT) is a well-known anticancer drug, which causes cancer cell apoptosis via the induction of DNA damage; however, the cytotoxicity of CPT easily reaches a plateau at a relatively high dose in lung cancer cells, thus limiting its efficacy. The present study demonstrated that CPT may induce autophagy in two human non‑small cell lung cancer cell lines, H1299 and H460. In addition, the results of a viability assay and Annexin V staining revealed that CPT-induced autophagy could protect lung cancer cells from programmed cell death. Conversely, the cytotoxicity of CPT was increased when autophagy was blocked by 3-methyladenine treatment. Furthermore, inhibition of autophagy enhanced the levels of CPT-induced DNA damage in the lung cancer cell lines. Accordingly, these findings suggested that autophagy exerts a protective role in CPT-treated lung cancer cells, and the combination of CPT with a specific inhibitor of autophagy may be considered a promising strategy for the future treatment of lung cancer.

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Sigma-Aldrich
4′,6-Diamidino-2-phenylindole dihydrochloride, BioReagent, suitable for fluorescence, ≥95.0% (HPLC)
Sigma-Aldrich
8-Cyclopentyl-1,3-dimethylxanthine, ≥98% (HPLC), powder
Sigma-Aldrich
3-Methyladenine, autophagy inhibitor