Synergisms of naturally-occuring products resveratrol and quercetin on cisplatin -induced cytotoxicity in lung cancer cells

• Main Authors: Yi Chin, 李易親
• Other Authors: Huei Lee
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/36251523080481444392

碩士 === 中山醫學大學 === 醫學分子毒理學研究所 === 99 === Cisplatin is frequently used for lung cancer chemotherapy. However, a high toxicity and side effects of cisplatin result in patients with poor outcome. How to reduce the toxicity and side effects of cisplatin is a very important medical issue. It is well documented that apoptostic and antiapoptotic gene expression are related with the resistance to cisplatin in cancer cells. In the present study, two polyphenols, resveratrol (RSV) and quercetin (QUE) were used to test 1) whether both compounds could synergistically increase cisplatin cytotoxicity to lung cancer cells; 2) which compound could have more effective; and 3) whether the changes of Bcl-2 family and apoptic gene expression by both compounds could be linked with increased cisplatin sensitivity? Four lung cancer cells (A549, H358, TL-1, and TL-4) were enrolled to evaluate their 50% inhibition concentration of cisplatin (IC50) by MTT assay. Data showed that the IC50 value of these four lung cancer cells was 11.1, 17.9, 21.6, and 26.6 μM, respectively. The IC50 was decreased to 8.7, 8.5 and 15.5 μM in A549, TL-1, and TL-4 cells when these cells were treated with RSV, but the change of IC50 was not observed in H358 cells. However, cisplatin sensitivity increased by QUE was only observed in A549 cells (17.7 vs. 11.3 μM), not in the other three cells. These results showed that cisplatin sensitivity increased by RSV is more effective than QUE. To verify which apoptosis-related genes could be linked with the cisplatin sensitivity, A549 and H358 cells were treated with RSV and QUE. Expressions of Mcl-1, XIAP, and Bcl-2 in A549 cells were markedly decreased by QUE in a dose-dependent manner; conversely, QUE elevated Bak expression. The gene expressions in H358 cells were not changed by QUE. As expected, the cisplatin sensitivity in A549 cells was signicantly increased by HA14-1, an inhibitor of Bcl-2 family, suggesting that the decrease of Mcl-1, XIAP, and Bcl-2 expressions by QUE could contribute to increased cisplatin sensitivity. In addition, Bak mRNA and protein expression markedly increased by QUE could partially contribute to cisplatin sensivity in A549 cells. This speculation should be further investigated.