The roles of traditional Chinese medicine in gene therapy

Ling, Changquan; Wang, Lina; Wang, Yuan; Zhang, Yuanhui; Yin, Zifei; Wang, Meng; Chen, Ling

doi:10.1016/s2095-4964(14)60019-4

Cited by 52 publications

(37 citation statements)

References 69 publications

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“…In our subsequent studies, we observed that rAAV3 vectors utilize the human hepatocyte growth factor receptor (hHGFR, also named c-Met) as a cellular coreceptor (Ling et al, 2010), which offered the potential opportunity to utilize rAAV3-based vectors for targeting human liver cancers, since hHGFR is overexpressed in most HCC cells (You et al, 2011). Furthermore, we (Ling et al, 2014a;Wang et al, 2014) and others (Zhang et al, 2010;Mitchell et al, 2013) have recently proposed the idea of using leading compounds isolated from traditional Chinese medicine (TCM) to enhance the efficacy of rAAV vector-based gene therapy. It is worth noticing that most natural drugs are multifunctional (Ling et al, 2014b) and therefore have the potential to play an additive, even synergistic, effect on rAAV vector-based cancer gene therapy.…”

Section: Introductionmentioning

confidence: 97%

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

et al. 2014

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Current challenges for recombinant adeno-associated virus (rAAV) vector-based cancer treatment include the low efficiency and the lack of specificity in vivo. rAAV serotype 3 (rAAV3) vectors have previously been shown to be ineffective in normal mouse tissues following systemic administration. In the present study, we report that rAAV3 vectors can efficiently target and transduce various human liver cancer cells in vivo. Elimination of specific surface-exposed serine and threonine residues on rAAV3 capsids results in further augmentation in the transduction efficiency of these vectors, without any change in the viral tropism and cellular receptor interactions. In addition, we have identified a potential chemotherapy drug, shikonin, as a multifunctional compound to inhibit liver tumor growth as well as to significantly enhance the efficacy of rAAV vector-based gene therapy in vivo. Furthermore, we also document that suppression of tumorigenesis in a human liver cancer xenograft model can be achieved through systemic administration of the optimized rAAV3 vectors carrying a therapeutic gene, and shikonin at a dose that does not lead to liver damage. Our research provides a novel means to achieve not only targeted delivery but also the potential for gene therapy of human liver cancer.

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Section: Introductionmentioning

confidence: 97%

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

et al. 2014

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“…In China, TCM practitioners are using a variety of techniques in an effort to treat diseases; TCM drugs have potential synergistic therapeutic effects with gene therapy in cancer treatments [15]. Currently, BC is categorized into luminal A, luminal B, Her-2-overexpressing, triple-negative, and normal subtypes.…”

Section: Discussionmentioning

confidence: 99%

Yiqi Formula Enhances the Antitumor Effects of Erlotinib for Treatment of Triple‐Negative Breast Cancer Xenografts

Liao

Zhou

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Yiqi formula (YF), a traditional herbal prescription, has long been used to treat triple-negative breast cancer (TNBC) patients. The present study aims to investigate the effects and the related mechanism of YF for treatment of TNBC xenografts. MDA-MB-231 (human TNBC) cells were subcutaneously injected into the second mammary fat pad of 40 female nude mice, which were divided into four groups: control, erlotinib (an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor), YF, and combination (YF plus erlotinib). All treatments were administered orally for 30 days. Inhibition rate of tumor weight by erlotinib, YF, and the combination was 26.47%, 17.24%, and 39.15%, respectively. Western blotting showed that YF, erlotinib, and the combination downregulated p-EGFR (P < 0.01) and p-Akt1 (pT308) (P < 0.05) and upregulated PTEN compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). Similar results were detected by immunohistochemistry. Real-time quantitative PCR showed that YF, erlotinib, and the combination increased PTEN mRNA (P < 0.05, P < 0.01) compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). In conclusion, YF can regulate the main components of the PI3K/Akt pathway in TNBC xenografts. When YF was used in combination with erlotinib, it enhanced the antitumor effects of erlotinib on TNBC xenografts. These findings suggest that YF is suitable to use for the treatment of TNBC patients.

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“…The treatment of natural products for metabolic diseases has not been explored in depth despite the fact that oral hypoglycemic agents, such as metformin, are derivatives of natural plant products [22,23]. Recently, the application of natural medicines or medicinal food for the treatment of liver disease and metabolic syndromes has been increasing in Asian countries because of their ability to protect hepatocytes through inhibiting hepatic inflammation and fibrosis in the liver [24][25][26]. Although several traditional medicines have been reported to be useful for the treatment of liver diseases, the molecular targets of such compounds have scarcely been identified in animal models [25,26].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the application of natural medicines or medicinal food for the treatment of liver disease and metabolic syndromes has been increasing in Asian countries because of their ability to protect hepatocytes through inhibiting hepatic inflammation and fibrosis in the liver [24][25][26]. Although several traditional medicines have been reported to be useful for the treatment of liver diseases, the molecular targets of such compounds have scarcely been identified in animal models [25,26]. Among numerous anti-obesity herbal medicines, Taeumjowitang (TH) is a decoction consisting of eight herbal ingredients which has traditionally been used as an herbal medicine in Korea to treat dyspepsia, stuffiness, the sensation of fullness, diarrhea, and wind stroke [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Hepatic proteome and its network response to supplementation of an anti-obesity herbal mixture in diet-induced obese mice

Kim

Park

Chaudhari

et al. 2015

Biotechnol Bioproc E

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In the present study, we investigated the effects of multi-herbal water extract mixture, Taeumjowi-tang (TH) on liver proteome alteration in mice using twodimensional electrophoresis combined with MALDI-TOF-MS. Animals were fed high-fat diet with or without TH (0.3% wt/wt) supplement for 12 weeks. At the end of 5 th week of experimental diet, mice fed high-fat diet only were subdivided into 2 groups, obesity-prone (OP) and obesityresistant (OR) mice based on weight gain. OR mice gained less body weight compared to OP mice despite of same food intake. TH significantly suppressed weight gain, and proteomic analysis enabled the identification of 49 liver proteins showing differential regulation between OP and OR/TH mice. Combined results of proteomic and western blot analyses revealed decreased lipogenesis via three fatty acid metabolic targets (AMPK, ACC, and FAS) in livers of OR and TH mice. Using bioinformatic classification and network analysis, most of the identified proteins were classified as hydrolases, oxidoreductases, transferases, defense/immunity proteins, and enzyme modulators based on functional analysis of the PANTHER classification system. Combined results of proteomic and bioinformatic analyses using GeneMANIA identified two proteins (LACTB2 and NIT2) in the liver that potentially interact with fatty acid metabolic proteins. Furthermore, these proteins were included in acetylation, phosphoprotein, and metabolic processes in DAVID classification. These proteins were highly expressed in OP mice; however both their transcription and protein expression were lowered by TH treatment. In conclusion, combined data from proteomic and network analyses suggest that TH exerts anti-obesity effects by modulating fatty acid metabolic proteins/genes, particularly via the AMPK pathway. Most targeted proteins/ genes were modulated toward enhancing lipid metabolism in response to TH treatment.

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The roles of traditional Chinese medicine in gene therapy

Cited by 52 publications

References 69 publications

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

SelectiveIn VivoTargeting of Human Liver Tumors by Optimized AAV3 Vectors in a Murine Xenograft Model

Yiqi Formula Enhances the Antitumor Effects of Erlotinib for Treatment of Triple‐Negative Breast Cancer Xenografts

Hepatic proteome and its network response to supplementation of an anti-obesity herbal mixture in diet-induced obese mice

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