Extracellular matrix (ECM) plays a pivotal and dynamic role in the construction of tumor microenvironment (TME), becoming the focus in cancer research and treatment. Multiple cell signaling in ECM remodeling contribute to uncontrolled proliferation, metastasis, immune evasion and drug resistance of cancer. Targeting trilogy of ECM remodeling could be a new strategy during the early-, middle-, advanced-stages of cancer and overcoming drug resistance. Currently nearly 60% of the alternative anticancer drugs are derived from natural products or active ingredients or structural analogs isolated from plants. According to the characteristics of ECM, this manuscript proposes three phases of whole-process management of cancer, including prevention of cancer development in the early stage of cancer (Phase I); prevent the metastasis of tumor in the middle stage of cancer (Phase II); provide a novel method in the use of immunotherapy for advanced cancer (Phase III), and present novel insights on the contribution of natural products use as innovative strategies to exert anticancer effects by targeting components in ECM. Herein, we focus on trilogy of ECM remodeling and the interaction among ECM, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), and sort out the intervention effects of natural products on the ECM and related targets in the tumor progression, provide a reference for the development of new drugs against tumor metastasis and recurrence.
Chelerythrine chloride (CHE) is a benzodiazepine alkaloid derived from natural herbs with significant anti‐tumor and anti‐inflammatory activities. However, the exact role and underlying mechanisms of CHE in colorectal cancer (CRC) remain unclear. Therefore, this study is aimed to investigate the influence of CHE on the progression of CRC. Cell Counting Kit‐8 assay (CCK‐8), transwell, apoptosis rate, cell cycle distribution, reactive oxygen species (ROS), and colony formation determined the anti‐proliferative activity of CHE in CRC cell lines. Transcriptome sequencing and western blot were used to explore the mechanism. Finally, H&E staining, Ki67, TUNEL, and immunofluorescence were conducted to verify the anti‐CRC activity and potential mechanisms of CHE in vivo. CHE had a prominent inhibitory effect on the proliferation of CRC cells. CHE induces G1 and S phase arrest and induces cell apoptosis by ROS accumulation. Cancer‐associated fibroblasts (CAFs) play a key role in CRC metastasis. Then, this study found that CHE regulates WNT10B/β‐catenin and TGFβ2/Smad2/3 axis, thereby decreasing the expression of α‐SMA, which is a maker of CAFs. Taken together, CHE is a candidate drug and a potent compound for metastatic CRC, which can intervene CAFs in a dual pathway to effectively inhibit the invasion and migration of cancer cells, which can provide a new choice for future clinical treatment.
Introduction:Cancer-related psychological disorders (CRPD) with high incidence are often underdiagnosed and undertreated. Although, some studies suggested that acupuncture and moxibustion (AM) are effective and safe for CRPD, lacking strong evidence, for instance, the relevant systematic review, meta-analysis, and randomized control trial (RCT) of a large sample, multicenter, makes the effects and safety remain uncertain. The aim of protocol is to evaluating the RCTs of AM for CRPD to verify the association of AM with the improvement of CRPD.Methods and analysis:Eight electric databases (4 English databases and 4 Chinese databases) will be searched from inception to Mar. 2022. There will be no restrictions on the category of the language. The RCTs of AM for CRPD unlimited to any type of cancer will be included. Depression and anxiety scores will be the primary outcome indicators. Two researchers will independently complete study selection, evaluate the risk of bias, and extract the data. The RevMan 5.2 software will be used to conduct data synthesis using the random-effects model. The weighted mean differences or standardized mean differences with 95% CIs will be used to present the results of measurement data, and the risk ratios with 95% CIs will be used to express the counting data. Additionally, we will use the Grading of Recommendations Assessment, Development, and Evaluation to assess evidence quality.Main results:The results of the meta-analysis will be presented with tables and figures.Ethics and dissemination:The results of this meta-analysis and meta-regression will be disseminated via publication in peer-reviewed journals and will be published at relevant conferences. The data to be used will not contain individual patient data; therefore, there is no need to worry about patient privacy.PROSPERO registration number:CRD42020177219.
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