| Summary: | 碩士 === 長榮大學 === 醫學研究所 === 94 === Our previous study showed that the crude extract from the leaves of Toona sinensis (TSL-CE) exerts potent anti-proliferative effect on A549 lung cancer cells. Since A549 is one of the Non-small-cell lung cancer (NSCLC) types, it is of interest to know whether TS also has anti-cancer effect on all three types of NSCLC. TSL-1, a fraction of TS crude extraction, is the supernatant parts of TSL-CE after centrifugation. The effects of TSL-1 on the proliferation of H441 cells (adenocarcinoma), H661 cells (large cell carcinoma) and H520 cells (squamous cell carcinoma) were investigated in this study. We tested the anti-cancer effect of TSL-1 on the proliferation and cell death. Our results showed that, the anti-proliferative effect of the TSL-1 is more potent than TSL-CE in all three cell types of NSCLC. Treatment of NSCLC cells with TSL-1 resulted in a G1-phase arrest by Flow cytometry. TSL-1 mediated G1 arrest was accompanied by the down-regulation of protein levels of cyclin-D1 in all three cell types of NSCLC, reduced cdk4 expression in H441 and H661, and the up-regulation of p27 in H520 and H661. We found that the decrease in cyclin D1 and cdk4 and the increase in p27 were most significant in H661 cells, compared to other two cell lines. Among the three cell lines, the IC50 for TSL-1 in H661 cells was the lowest, indicating the anti-cancer effect of TSL-1 is most potent in this cell line. TSL-1-induced apoptosis was confirmed by cell morphology, Sub-G1 peak accumulation, cleavage of PARP, PI-Annexin-V double staining and TUNEL assay in all three types of NSCLC. Adenocarcinoma of the lung cancer is now the most worldwide common subtype of NSCLC. Therefore, we performed in vivo experiments to evaluate the therapy and prevention effects of TSL-1 on H441 cells. Per os and intraperitoneal treatment of TSL-1 was used in therapy study, while only per os treatment of TSL-1 was used in prevention study. Our results revealed that treatment of TSL-1 inhibits H441 tumor growth in either therapy or prevention experiments. Whereas, TSL-1 did not show any side effects in these in vivo studies. Our results suggest that TSL-1 could be used as a health food for preventing and alleviating lung cancer proliferation and possess the potential to be developed as an anticancer drug.
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