Dataset Information

The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer.

ABSTRACT: Over the past decade, natural compounds have been proven to be effective against many human diseases, including cancers. Triptolide (TPL), a diterpenoid triepoxide from the Chinese herb Tripterygium wilfordii Hook F, has exhibited attractive cytotoxic activity on several cancer cells. An increasing number of studies have emphasized the antitumor effects of TPL on non-small cell lung cancer (NSCLC). Here we mainly focused on the key molecular signaling pathways that lead to the inhibitory effects of TPL on human NSCLC, such as mitogen-activated protein kinases (MAPKs) modulation, inhibition of NF-?B activation, suppression of miRNA expression, etc. In addition, the effect of TIG on immune response in cancer patients is summarized for improved immune modulation utilization. However, the clinical use of TPL is often limited by its severe toxicity and water insolubility. Future clinical trials and drug delivery strategies that will evaluate the security and validate the underlying tumor-killing properties of TPL in human NSCLC are also to be discussed.

SUBMITTER: Wei J

PROVIDER: S-EPMC7848329 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer.

Wei Jie J Yan Yuanliang Y Chen Xi X Qian Long L Zeng Shuangshuang S Li Zhi Z Dai Shuang S Gong Zhicheng Z Xu Zhijie Z

Oncology research 20190408 7

Over the past decade, natural compounds have been proven to be effective against many human diseases, including cancers. Triptolide (TPL), a diterpenoid triepoxide from the Chinese herb <i>Tripterygium wilfordii</i> Hook F, has exhibited attractive cytotoxic activity on several cancer cells. An increasing number of studies have emphasized the antitumor effects of TPL on non-small cell lung cancer (NSCLC). Here we mainly focused on the key molecular signaling pathways that lead to the inhibitory ...[more]

PMID: 30982492

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Project description:ObjectivePatient-derived xenograft (PDX) models have shown great promise in preclinical and translational applications, but their consistency with primary tumors in phenotypic, genetic, and pharmacodynamic heterogeneity has not been well-studied. This study aimed to establish a PDX repository for non-small cell lung cancer (NSCLC) and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.MethodsA total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice. Based on the successful establishment of the NSCLC PDX model, we compared the expressions of vimentin, Ki67, EGFR, and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining. In addition, we detected whole gene expression profiling between primary tumors and PDX generations. We also performed whole exome sequencing (WES) analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities. Finally, paclitaxel, cisplatin, doxorubicin, atezolizumab, afatininb, and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.ResultsA large collection of serially transplantable PDX models for NSCLC were successfully developed. The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients' tumor samples. WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors. Similar to clinical patients, PDX models responded differentially to the standard-of-care treatment, including chemo-, targeted- and immuno-therapeutics.ConclusionsOur established PDX models of NSCLC faithfully reproduced the molecular, histopathological, and therapeutic characteristics, as well as the corresponding tumor heterogeneities, which provides a clinically relevant platform for drug screening, biomarker discovery, and translational research.

Dataset Information

The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer.

Publications

The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer.

Similar Datasets

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