Salidroside Promotes Sensitization to Doxorubicin in Human Cancer Cells by Affecting the PI3K/Akt/HIF Signal Pathway and Inhibiting the Expression of Tumor-Resistance-Related Proteins.
Yonghua ZhanXu NieLi LiHui-Fang LiuYang-Yao PengWang-Ting ZhouXiao-Jia HuXin-Yi XuXue-Li ChenPublished in: Journal of natural products (2022)
Salidroside (Sal), the major active constituent of Rhodiola rosea L., is considered as a potential pro-drug with various activities; however, its role in tumor therapy is not clear. Here, we demonstrated in vitro and in vivo that Sal enhanced the inhibitory activity of doxorubicin (DOX) in drug-resistant cancer cell lines. Our results showed that combination drug treatment (Sal and DOX) significantly decreased cell proliferation, migration, and motility. Besides biological validation, a luciferase-labeled animal tumor xenograft model and bioluminescence imaging (BLI) were applied for assessing the tumor progression. Sal combined with DOX inhibited the growth of HeLa-ADR-luc cells in vivo and downregulated the DOX-induced high expression of MDR1. Also, Sal downregulated the Bcl-2, MMP-2, MMP-9, PI3K, and AKT and upregulated BAX proteins. Sal demonstrated high safety and cardiac protection activity. We discovered that Sal enhances DOX sensitivity through the regulation of PI3K/Akt/HIF-1α and DOX-induced resistance pathways. Our results suggest that Sal could be a novel chemosensitization agent for the treatment of multi-drug-resistance tumors.
Keyphrases
- cell proliferation
- drug resistant
- pi k akt
- signaling pathway
- cell cycle arrest
- poor prognosis
- endothelial cells
- induced apoptosis
- multidrug resistant
- high glucose
- drug induced
- diabetic rats
- drug delivery
- acinetobacter baumannii
- high resolution
- adverse drug
- heart failure
- long non coding rna
- cell death
- left ventricular
- cancer therapy
- young adults
- anti inflammatory
- escherichia coli
- biofilm formation
- computed tomography
- pseudomonas aeruginosa
- risk assessment
- bone marrow
- staphylococcus aureus
- fluorescence imaging
- cell therapy
- quantum dots
- induced pluripotent stem cells