Student Research Committee and Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Cellular and Molecular Research Center, Birjand University of Medical Sciences, P.O. Box 9717853577, Birjand, Iran.
Mol Cell Biochem. 2021 Sep;476(9):3341-3351. doi: 10.1007/s11010-020-04043-8. Epub 2021 Apr 30.
Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice's weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.
转移性乳腺癌仍然是一个严重的健康问题，许多研究推荐药用植物作为一种补充疗法。藏红花素是一种已知的抗癌生物成分。最近，二甲双胍在癌症的各个方面的抑制作用已经被研究。然而，没有研究报道它们在转移性乳腺癌中的联合作用。在本研究中，我们评估了它们在体外和体内乳腺癌模型中的抗转移作用。通过 MTT 检测、划痕和黏附试验，我们分别评估了藏红花素和二甲双胍对 4T1 细胞系的细胞毒性、抗侵袭和抗黏附作用。在 4T1 小鼠乳腺癌模型中研究了它们的保护作用以及 MMP9 和 VEGF 蛋白的表达水平（Western blot）。我们的结果表明，藏红花素和二甲双胍均可降低细胞活力，延缓划痕愈合，并抑制细胞黏附，在体外。虽然单独的藏红花素恢复了小鼠的体重减轻，但藏红花素、二甲双胍及其组合可显著减小肿瘤体积大小并提高小鼠乳腺癌模型中的动物存活率，这些反应与 VEGF 和 MMP9 的下调有关。这些发现表明，藏红花素和二甲双胍的联合应用可能成为增强转移性乳腺癌治疗效果的一种新的治疗方法。
