目的 探究堆心菊灵在人前列腺癌细胞中的抗癌作用及其潜在的作用机制。方法 人前列腺癌DU145和PC-3细胞分别以不同浓度的堆心菊灵处理48 h，CCK-8法检测细胞存活率；qRT-PCR法检测硫氧还蛋白还原酶1（thioredoxin reductase 1，TrxR1）mRNA表达情况。从人类蛋白免疫组化表达数据库中检测前列腺癌组织和正常组织中TrxR1蛋白表达情况；经堆心菊灵或活性氧（reactive oxygen species，ROS）抑制剂处理后，采用DCFH-DA染色法检测ROS的产生；敲除或过表达TrxR1，经堆心菊灵处理后，检测2种细胞中ROS水平。结果 堆心菊灵显著抑制前列腺癌细胞存活率和TrxR1 mRNA表达水平（P＜0.05、0.001），呈剂量相关性。与正常组织相比，TrxR1在前列腺癌组织中高表达。堆心菊灵显著诱导了前列腺癌细胞中ROS的产生，敲除TrxR1显著提高了前列腺癌细胞中ROS水平，过表达TrxR1抑制了前列腺癌细胞中ROS产生；而堆心菊灵可改善TrxR1过表达对ROS产生的抑制作用。结论 堆心菊灵可以通过靶向人前列腺癌细胞中的TrxR1来促进ROS的产生，进而发挥抗前列腺癌的作用。

Objective To explore the anticancer effect and potential mechanism of helenalin in human prostate cancer cells. Methods Human prostate cancer DU145 and PC-3 cells were treated with different concentrations of helenalin for 48 h, and cell viability was detected by CCK-8 method, thioredoxin reductase 1 (TrxR1) mRNA expression was detected by qRT-PCR method. The protein expression of TrxR1 in prostate cancer tissues and normal tissues was detected by human protein immunohistochemical expression database; After treated with helenalin or reactive oxygen species (ROS) inhibitors, the production of ROS was detected by DCFH-DA staining; Knockout or overexpression of TrxR1, ROS levels in two kinds of cells after treated with helenalin were detected. Results Helenalin significantly inhibited the survival rate of prostate cancer cells and TrxR1 mRNA expression (P < 0.05, 0.001), with a concentration-dependent manner. Compared with normal tissues, TrxR1 is highly expressed in prostate cancer tissues. Helenalin significantly induced ROS production in prostate cancer cells, knockdown of TrxR1 significantly increased ROS level in prostate cancer cells, and overexpression of TrxR1 inhibited the production of ROS in prostate cancer cells. Conclusion Helenalin can promote the production of ROS by targeting TrxR1 in human prostate cancer cells, thereby exerting an anti-prostate cancer effect.

R285.5

温州市科技计划经费自筹项目(Y20180481)