Xiaoaiping injection enhances paclitaxel efficacy in ovarian cancer via pregnane X receptor and its downstream molecules

Zhang, Xiangqi; Ding, Ya-Wei; Chen, Junjun; Xiao, Xiao; Zhang, Wei; Zhou, Li; Kong, Qian-Wen; Shi, Mei-Zhi; Jiao, Yang; Jiang, Bo; Guo, Cheng; Han, Yonglong

doi:10.1016/j.jep.2020.113067

Cited by 16 publications

(7 citation statements)

References 35 publications

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“…Firstly, Xiao-ai-ping alone (particularly via injection route) exhibits direct anticancer effect in different cancer cell lines and animal tumor xenografts 47 , 48 . Secondly, the injectable Xiao-ai-ping enhances the antitumor effects of several anticancer drugs through various mechanisms including the inhibition of CYP3A4 activity, downregulation of activating transcription factor 3 (ATF3), and suppression of pregnane X receptor (PXR) expression and downstream targets 49 , 50 , 51 . Moreover, our research team also reported that several POPs in M. tenacissima inhibited the MDR ABC transporters and potentiated the cytotoxic effect of chemotherapeutic drugs previously 24 .…”

Section: Discussionmentioning

confidence: 99%

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

Yin

et al. 2021

Acta Pharmaceutica Sinica B

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Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima ( M. tenacissima ) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression, which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity. These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay, and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo . We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance. The results suggested that these POPs had the potential to be developed as safe, potent, and specific pro-drugs to reverse ABCB1-mediated MDR. Our work also provided scientific evidence for the use of M. tenacissima in combinational chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

Yin

et al. 2021

Acta Pharmaceutica Sinica B

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“…For example, MTE combined with cisplatin significantly reduced the invasion and migration of ovarian cancer cells ( 6 ). It enhances paclitaxel efficacy in ovarian cancer by suppressing the expression of the pregnane X receptor and its downstream molecules ( 7 ). MTE also has an immune regulatory effect on the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer

Yi,

Zhang,

Yan

et al. 2023

Front. Immunol.

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IntroductionTumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear.MethodWe collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors.ResultsUnder single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models.ConclusionsOur findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.

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“…Fuzheng Kang Ai decoction combined with erlotinib enhances the effect of lung cancer treatment [ 21 ]. Xiaoaiping injection enhanced paclitaxel efficacy in ovarian cancer proliferation by inhibiting pregnane X receptor [ 22 ]. Huyang Yangkun Formula could enhance the therapeutic effect of embryonic stem cells on premature ovarian failure mice.…”

Section: Introductionmentioning

confidence: 99%

Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

Qiao

Zhang

et al. 2021

Chin Med

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Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P < 0.05 or P < 0.001). Besides, the combination group markedly inhibited the levels of IL-1β, IL-6, and TNF-α in hippocampus (P < 0.001), as well as activities of SOD, CAT, and GSH-Px in serum (P < 0.001). By contrast, the combination group improved synaptic plasticity by enhancing SYN, PSD95, and GAP43 expression. Conclusions Taken together, these data supported the notion that CG combined with Mm might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity.

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Xiaoaiping injection enhances paclitaxel efficacy in ovarian cancer via pregnane X receptor and its downstream molecules

Cited by 16 publications

References 35 publications

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer

Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

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