文献类型：期刊文献

英文题名：Synergistic anticancer effects of andrographolide and paclitaxel against A549 NSCLC cells

作者：Yuan, Huihui[1];Sun, Bo[1];Gao, Feng[2];Lan, Minbo[1,3]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai Key Lab Funct Mat Chem, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China

年份：2016

卷号：54

期号：11

起止页码：2629

外文期刊名：PHARMACEUTICAL BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000386041900032)】；

基金：The authors report that they have no conflicts of interest. This work was financially supported by the Science and Technology Commission of Shanghai Municipality (STCSM, Contract no. 11nm0505700).

语种：英文

外文关键词：Antiproliferation; apoptosis; cell cycle; ROS; antitumour

摘要：Context: Paclitaxel (PTX) is widely used in chemotherapy for cancer treatment; however, it has some serious side effects. Andrographolide (Andro) is a potential cancer therapeutic agent isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae).Objective: The objective of this study is to evaluate the effects of PTX combined with Andro against A549 cells.Materials and methods: The effects of 24-48h treatment with 0.48-60.75nM PTX and 5.10-328.0M Andro on cellular proliferation, apoptosis, cell cycle and intracellular reactive oxygen species (ROS) were determined by sulphorhodamine B assay, Annexin V-FITC/PI apoptosis detection, PI staining and ROS assay, respectively. Synergy was determined using combination index. The antitumour efficacy of 20mg/kg PTX with 100mg/kg Andro was studied in a xenograft murine model.Results: IC50 value of the PTX combined with Andro against A549 cells was 0.5-7.4nM, which was significantly lower than that of PTX (15.9nM). PTX with 10M Andro caused (1.22-1.27)-fold apoptosis and 1.7-fold ROS accumulation compared with PTX alone. N-Acetylcysteine, a ROS scavenger, blocked this synergy in vitro. In contrast, G2/M phase cell cycle arrest resulting from PTX was not potentiated by Andro. Moreover, PTX in combination with Andro inhibited the growth of A549 transplanted tumours by 98%.Discussion and conclusion: The results indicate that the combination of PTX and Andro exert significant synergistic anticancer effect on A549 cells in vitro and in vivo. The synergy may be the result of the accumulation of ROS. The combination of Andro and PTX represents a potential strategy for the treatment of A549 cells.