Multi-omics joint analysis reveals the mechanism of action of the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Moon in the treatment of hepatocellular carcinoma

Li, Siyu; Pei, Wei; Yuan, Wei; Yu, Dan; Song, Huanjie; Zhang, Hui

doi:10.1016/j.jep.2022.115285

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…Interestingly, there are few clues that MTE inhibits angiogenesis by downregulation of VEGF signaling previously ( Wang et al, 2016 ; Dai et al, 2017 ). The molecular network profiling and multi-omic joint analyses using an H22 mouse model of HCC have suggested that MTE might inhibit angiogenesis by targeting HIF1α ( Li et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Extract of Marsdenia tenacissima (Roxb.) Moon [Apocynaceae] Suppresses Hepatocellular Carcinoma by Inhibiting Angiogenesis

et al. 2022

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The extract of Marsdeniatenacissima (Roxb.) Moon [Apocynaceae] (MTE) has shown a significant anti-cancer effect on hepatocellular carcinoma (HCC), but its mechanism remains unclear. In this study, we used transcriptomics methods to investigate the underlying mechanism of MTE against HCC. Both MHCC97H and HepG2 cell lines were treated with MTE. The cell viability and migration were measured using the cell counting kit-8 assay and transwell assay. RNA-sequencing was used to identify differentially expressed genes (DEGs) between HepG2 cells treated with and without MTE. The expression levels of selected DEGs—vascular endothelial growth factor-A (VEGFA), platelet-derived growth factor receptor-β (PDGFRB), and von Willebrand factor (VWF)—were verified by RT-PCR and Western blot. The effect of conditioned medium from HCC cells with MTE treatment (CM-MTE) on blood vessels was observed by tube formation assay of HUVECs and chick chorioallantoic membrane (CAM) assay. A mouse model of HCC patient-derived tumor xenograft (PDX) was established and treated with MTE. The effect of MTE on the growth and angiogenesis of HCC-PDX was analyzed. The results demonstrated that MTE inhibited the viability and migration of HCC cells. RNA-seq showed that MTE treatment downregulated multiple genes associated with metabolism and angiogenesis. The expression levels of VEGFA, VWF, PDGFB, and PDGFRB in HCC cells were significantly suppressed by MTE. Meanwhile, MTE effectively inhibited the tube-forming capability of HUVECs and the angiogenesis of chick CAM. In vivo experiments revealed that the extract reduced tumor volume, inhibited the proliferation of HCC cells, and expanded the necrotic area of the tumor. Immunohistochemical results showed that the expression levels of CD31, PDGFB, VEGF, VWF, and PDGFRB in the HCC-PDX tumor tissues were all downregulated by MTE in a dose-dependent manner. Taken together, MTE could inhibit angiogenesis by repressing the expression of VEGF, VWF, PDGF, and PDGFRB in HCC cells, a mechanism that may enable MTE to counter HCC development.

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Section: Discussionmentioning

confidence: 99%

Extract of Marsdenia tenacissima (Roxb.) Moon [Apocynaceae] Suppresses Hepatocellular Carcinoma by Inhibiting Angiogenesis

et al. 2022

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“…Moon and explored active components and identified anti-tumor targets. Tenacissosides I, H, and G were active ingredients for hepatocellular carcinoma treatment, and could inhibit angiogenesis, promote apoptosis, and improve immune function, respectively, which exerts beneficial effects of multi-components and multi-targets [43]. Therapeutic mechanism of a traditional patent drug Tripterygium Wilfordii Hook F pills for immunological non-responders treatment was investigated using multi-omics, and found it regulated great majority of down-regulated genes, and triptolide as bioactivity compound, inhibited IFN-γ production and immune cell activation as well as expression of downstream genes [44].…”

Section: Multi-omics Strategiesmentioning

confidence: 99%

Multi-omics technology for demystifying herbal medicine

Zhang¹,

Qiu²

2023

Adv. Mater. Lett.

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“…Marsdenia tenacissima, also known as glaucescent fssistigma root, Rosa banksiae f. lutea (Lindl.) Rehd, etc., is the dry stem and rattan of Marsdenia tenacissima (Roxb) Wight et Am., a plant belonging to the family Asclepiadaceae [1][2][3], which was originally published in the Herbal Medicines of Southern Yunnan and is now published in the Chinese Pharmacopoeia 2010 edition [4,5]. It is mainly distributed in Guizhou, Yunnan, Sichuan, Guangxi, and other places.…”

Section: Introductionmentioning

confidence: 99%

Determination of Tenacissoside G, Tenacissoside H, and Tenacissoside I in Rat Plasma by UPLC-MS/MS and Their Pharmacokinetics

Chen,

Ma,

Cui

et al. 2023

International Journal of Analytical Chemistry

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An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of tenacissoside G, tenacissoside H, and tenacissoside I in rat plasma. The rat plasma was treated with liquid-liquid extraction using ethyl acetate. The determination was performed on the UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 μm) with a mobile phase consisting of acetonitrile-water (containing 0.1% formic acid) and gradient elution at a flow rate of 0.4 mL/min. Electrospray (ESI) positive ion mode detection and multireaction monitoring (MRM) quantitative analysis were performed. A total of 36 rats were given tenacissoside G, tenacissoside H, and tenacissoside I, respectively, orally (5 mg/kg) and intravenously (1 mg/kg), with 6 rats in each group, to evaluate the pharmacokinetic difference of tenacissoside G, tenacissoside H, and tenacissoside I in rats. The calibration curves showed good linearity in the range of 5–2000 ng/mL, where r was greater than 0.99. The results of precision, accuracy, recovery, matrix effect, and stability met the requirements of biological sample detection methods. The established UPLC-MS/MS method was successfully applied to pharmacokinetic studies of tenacissoside G, tenacissoside H, and tenacissoside I, and the bioavailability was 22.9%, 89.8%, and 9.4%, respectively.

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Multi-omics joint analysis reveals the mechanism of action of the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Moon in the treatment of hepatocellular carcinoma

Cited by 7 publications

References 43 publications

Extract of Marsdenia tenacissima (Roxb.) Moon [Apocynaceae] Suppresses Hepatocellular Carcinoma by Inhibiting Angiogenesis

Extract of Marsdenia tenacissima (Roxb.) Moon [Apocynaceae] Suppresses Hepatocellular Carcinoma by Inhibiting Angiogenesis

Multi-omics technology for demystifying herbal medicine

Determination of Tenacissoside G, Tenacissoside H, and Tenacissoside I in Rat Plasma by UPLC-MS/MS and Their Pharmacokinetics

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