LncRNA TSLNC8 synergizes with EGFR inhibitor osimertinib to inhibit lung cancer tumorigenesis by blocking the EGFR-STAT3 pathway.
Cell cycle (Georgetown, Tex.)
The roles of lncRNA TSLNC8 and its synergetic effects with osimertinib remain unknown in lung cancer. qRT-PCR or western blotting was performed to determine the expression levels of TSLNC8, EGFR and STAT3. Colony formation and MTT assays were used to evaluate cell proliferation. Transwell and wound healing assays were performed to assess migration and invasion abilities. Flow cytometry with Annexin V/PI staining was used to detect changes in cell apoptosis. Nude mice subcutaneous tumor model was constructed and used for validating the effects of TSLNC8 and osimertinib . Expression of TSLNC8 was down-regulated in clinical lung cancer tissues and cell lines. TSLNC8 overexpression or osimertinib administration led to promotion of apoptosis and inhibition of cell proliferation, migration and invasion, as well as deactivation of the EGFR-STAT3 pathway, whereas TSLNC8 knockdown had opposite effects. Moreover, the above effects of osimertinib were remarkably enhanced by TSLNC8 overexpression and inhibited by TSLNC8 knockdown, respectively. Meanwhile, the effects of TSLNC8 overexpression were reversed by STAT3 activation or EGFR overexpression. In the animal model, combination of TSLNC8 overexpression and osimertinib administration resulted in efficient suppression of tumor growth. In this study, we revealed a TSLNC8-EGFR-STAT3 signaling axis in lung cancer, and TSLNC8 overexpression significantly enhanced the anti-tumor effects of osimertinib via inhibiting EGFR-STAT3 signaling.
10.1080/15384101.2020.1820697
Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor.
Tan Tao,Wang Yuqi,Wang Jing,Wang Zhiwan,Wang Hong,Cao Haiqiang,Li Jie,Li Yaping,Zhang Zhiwen,Wang Siling
Acta pharmaceutica Sinica. B
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
10.1016/j.apsb.2019.05.006
Bioinspired lipoproteins-mediated photothermia remodels tumor stroma to improve cancer cell accessibility of second nanoparticles.
Tan Tao,Hu Haiyan,Wang Hong,Li Jie,Wang Zhiwan,Wang Jing,Wang Siling,Zhang Zhiwen,Li Yaping
Nature communications
The tumor stromal microenvironments (TSM) including stromal cells and extracellular matrix (ECM) form an abominable barrier hampering nanoparticles accessibility to cancer cells, significantly compromising their antitumor effects. Herein, we report a bioinspired lipoprotein (bLP) that can induce efficient photothermia to remodel TSM and improve second bLP accessibility to cancer cells for antitumor therapy. The multiple stromal cells and ECM components in TSM are remarkably disrupted by bLP-mediated photothermal effects, which cause a 4.27-fold enhancement of second bLP accumulation in tumor, deep penetration in whole tumor mass and 27.0-fold increase of accessibility to cancer cells. Of note, this bLP-mediated TSM-remodeling to enhance cancer cell accessibility (TECA) strategy produces an eminent suppression of tumor growth and results in a 97.4% inhibition of lung metastasis, which is superior to the counterpart liposomes. The bLP-mediated TECA strategy provides deeper insights into enhancing nanoparticle accessibility to cancer cells for antitumor therapy.
10.1038/s41467-019-11235-4
[Serum metabolomics of chronic obstructive pulmonary disease with lung-Qi deficiency syndrome].
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.
10.19540/j.cnki.cjcmm.20211203.501
Tumor-permeated bioinspired theranostic nanovehicle remodels tumor immunosuppression for cancer therapy.
Wang Hong,Li Jie,Wang Zhiwan,Wang Yuqi,Xu Xiaoxuan,Gong Xiang,Wang Jiaoying,Zhang Zhiwen,Li Yaping
Biomaterials
The robust immunosuppressive microenvironment in tumor represents a key challenge of cancer treatment, and their modulations by versatile therapeutic agents are critically hampered by the limited intratumoral delivery. Herein, we report a bioinspired tumor-responsive theranostic nanovehicle (BTN) with striking tumor-penetrating capability to relieve the profound immunosuppression in tumor for effective cancer therapy. BTN is designed by loading tumor-activated melittin pro-peptide, theranostic photochlor and reactive oxygen species (ROS)-responsive prodrug of chemo-immunomodulator gemcitabine into a bioinspired lipoprotein-based nanovehicle, which display prominent tumor accumulation and flexible intratumoral permeation. Notably, the BTN-mediated combinational treatment caused drastic elimination of multiple immunosuppressive cells and remarkable infiltration of cytotoxic lymphocytes in tumor, thereby essentially relieving the tumor immunosuppression and strikingly depressing the tumor growth. Therefore, this design provides an encouraging delivery nanoplatform with distinguished immunosuppression-relieving capacity for effective cancer therapy.
10.1016/j.biomaterials.2020.120609
Guideline on Establishing Diagnostic Criteria for Chinese Medicine Syndromes.
Journal of evidence-based medicine
AIM:To formulate the guideline for the development of diagnostic criteria for Chinese medicine syndromes, which can contribute to standardization of development of Chinese medicine syndrome diagnostic standards. METHODS:We embark into account on the development of Guideline on Establishing Diagnostic Criteria for Chinese Medicine Syndromes through Delphi method with reference to the existing technical system of diagnostic criteria for Chinese medicine syndromes and relevant criteria. RESULTS:Our guideline specifies principles, methods, and procedures for the formulation of diagnostic criteria for Chinese medicine syndromes. CONCLUSIONS:It is a comprehensive and systematic evidence-based guideline, and we hope this guideline can be applied as a reference in developing diagnostic criteria for Chinese medicine syndromes in other disciplines. It is also applicable to the formulation of diagnostic criteria for relevant clinical, educational, and scientific research by hospitals, institutes, and academies.
10.1111/jebm.12572
Oxygen-Delivering Polyfluorocarbon Nanovehicles Improve Tumor Oxygenation and Potentiate Photodynamic-Mediated Antitumor Immunity.
Wang Zhiwan,Gong Xiang,Li Jie,Wang Hong,Xu Xiaoxuan,Li Yaping,Sha Xianyi,Zhang Zhiwen
ACS nano
Hypoxia is a critical cause of tumor immunosuppression, and it significantly limits the efficacy of many anticancer modalities. Herein, we report an amphiphilic F-derivative-based oxygen-delivering polyfluorocarbon nanovehicle loading photodynamic DiIC(5) and reactive oxygen species (ROS)-sensitive prodrug of chemo-immunomodulatory gemcitabine (PFDG), aimed at relieving tumor hypoxia and boosting antitumor immunity for cancer therapy. We optimized F-based polyfluorocarbon nanovehicles with a 10-fold enhancement of tumor oxygenation. PFDG exhibited intriguing capabilities, such as oxygen-dissolving, ROS production, and responsive drug release. In tumors, PFDG exhibited flexible intratumoral permeation and boosted robust antitumor immune responses upon laser irradiation. Notably, the treatment of PFDG plus laser irradiation (PFDG+L) significantly retarded the tumor growth with an 82.96% inhibition in the 4T1 breast cancer model and a 93.6% inhibition in the PANC02 pancreatic cancer model with better therapeutic benefits than non-oxygen-delivering nanovehicles. Therefore, this study presents an encouraging polyfluorocarbon nanovehicle with deep tumor-penetrating and hypoxia-relieving capacity to boost antitumor immunity for cancer treatment.
10.1021/acsnano.1c00033