Abstract
We investigated the antitumor effects of four fractions of Dendrobium officinale Kimura & Migo (D. officinale) polysaccharides with different molecular weights (Mw), Astragalus membranaceus polysaccharides (APS) and Lentinus edodes polysaccharides (LNT) on colorectal cancer (CRC) using a zebrafish xenograft model. Transcriptome sequencing was performed to further explore the possible antitumor mechanisms of D. officinale polysaccharides. Fractions of D. officinale polysaccharides, LNT, and APS could significantly inhibit the growth of HT-29 cells in a zebrafish xenograft model. One fraction of D. officinale polysaccharides called DOPW-1 (Mw of 389.98 kDa) exhibited the strongest tumor inhibition. Compared with the control group, RNA-seq revealed that the DOPW-1–treated experimental group had 119 differentially expressed genes (DEGs), of which 45 had upregulated expression and 74 had downregulated expression. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes suggested that the pathway “apoptosis-multiple species” was the most significantly enriched. Our data indicated that 1) fractions of D. officinale polysaccharides of Mw 389.98 kDa were most suitable against CRC; 2) DOPW-1 could be developed into a clinical agent against CRC; and 3) an apoptosis pathway is important for DOPW-1 to inhibit the proliferation of HT-29 cells.
Highlights
Dendrobium officinale Kimura & Migo (D. officinale) is a perennial herb in the Orchidaceae family
We evaluated the changes in the gene-expression profile induced by treatment with D. officinale polysaccharides on HT-29 cells by RNA sequencing (RNA-seq) to explore the underlying anti-colorectal cancer (CRC) mechanism
The dose of 5-Fu was selected based on the study by Xu et al (2019), and the dose of experimental groups was selected based on our previous study (Tao et al, 2021), where we explored the maximum tolerance concentration (MTC) of polysaccharides from D. officinale and determined the effect of polysaccharides from D. officinale (27.8, 83.3, 250 μg·ml−1) in the zebrafish xenograft model
Summary
Dendrobium officinale Kimura & Migo (D. officinale) is a perennial herb in the Orchidaceae family. It possesses high pharmacological value and nutritional value. Few studies have focused on the activity of D. officinale polysaccharides against colorectal cancer (CRC). Wang et al (2014) showed that high-Mw polysaccharides (524 kDa) from Lentinus edodes displayed robust antitumor effects. Ren et al (2016) revealed that a high-Mw polysaccharide (463 kDa) from Pleurotus eryngii had antitumor effects against HepG2 cells. Xu et al (2016) revealed that medium-Mw polysaccharides (rather than high-Mw polysaccharides) from Camellia-species seed cake displayed excellent antioxidant activity. Zhang et al (2019) explored the suitable Mw range of polysaccharides from D. officinale on inducing the apoptosis of HeLa cells, but was studied in vitro only. For CRC, the Mw of D. officinale polysaccharides that are most suitable in vivo is still unknown
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