Zhang Ailian, Li Jincheng
1 Department of Rehabilitation Medicine, The First Hospital Affiliated of Liaoning Medical University, Jinzhou, China.
2 Department of Breast Surgery, The First Hospital Affiliated of Liaoning Medical University, Jinzhou, China.
Tumour Biol. 2017 Mar;39(3):1010428317694536. doi: 10.1177/1010428317694536.
The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.
氟尿嘧啶化疗并非总是有效，部分乳腺癌细胞可能通过增强自噬在氟尿嘧啶治疗中存活下来。西红花酸是中药藏红花的主要成分，最近发现它具有多种药理作用，包括抗癌作用。然而，西红花酸对乳腺癌氟尿嘧啶治疗效果的影响尚未得到研究。在此，我们发现，在细胞计数试剂盒8检测法或MTT检测法中，氟尿嘧啶治疗均能抑制乳腺癌细胞的生长。抑制自噬进一步抑制了乳腺癌细胞的生长，这表明乳腺癌细胞在氟尿嘧啶治疗期间通过自噬提高了细胞存活率。然而，西红花酸显著增强了氟尿嘧啶对乳腺癌细胞生长的抑制作用，且不影响细胞凋亡或自噬。在存在西红花酸的情况下抑制自噬，部分消除了对乳腺癌细胞生长的抑制作用，这表明西红花酸可能会增加氟尿嘧啶处理的乳腺癌细胞中的自噬性细胞死亡。此外，西红花酸降低了氟尿嘧啶处理的乳腺癌细胞中Beclin-1的水平，但提高了ATG1的水平。总之，这些数据表明，西红花酸可能会使氟尿嘧啶处理的乳腺癌细胞中的自噬性细胞存活转变为自噬性细胞死亡，这可能是通过调节ATG1和Beclin-1的表达来实现的。
