A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis.

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.

Predictive impact of sarcopenia in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: A retrospective study.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18-75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265-0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Single-cell RNA sequencing reveals that the immunosuppression landscape induced by chronic stress promotes colorectal cancer metastasis.

The high prevalence of depressive disorders in individuals with cancer and their contribution to tumour progression is a topic that is gradually gaining attention. Recent evidence has shown that there are prominent connections between immune gene variants and mood disorders. The homeostasis of the tumour immune microenvironment (TIME) and the infiltration and activation of immune cells play a very important role in the antitumour effect. In this study, we established a compound mouse model with chronic unpredictable mild stress (CUMS) and orthotopic colorectal cancer to simulate colorectal cancer (CRC) patients with depression. Using 10✕Genomics single-cell transcriptome sequencing technology, we profiled nearly 30,000 cells from tumour samples of 8 mice from the control and CUMS groups, revealed that immune cells in tumours under a chronic stress state trend toward a more immunosuppressive and exhaustive status, and described the crosstalk between the overall inflammatory environment and immunosuppressive landscape to provide mechanistic information or efficacious strategies for immune-oncology treatments in CRC with depressive disorders.

The Role of Zuo Jin Wan in Modulating the Tumor Microenvironment of Colorectal Cancer.

INTRODUCTION: Traditional Chinese medicine (TCM) can modulate the immune function of tumor patients in various ways. Zuojin Wan (ZJW, a 6:1 ratio of Huanglian and Wuzhuyu) can modulate the microenvironment of ulcerative colitis, but its role in regulating the CRC microenvironment remains unclear. Exploring the role of ZJW in CRC immunomodulation may improve the antitumor effect of existing immunotherapeutic strategies. MATERIAL AND METHODS: The active compounds of each herb in ZJW were obtained from the HIT2.0 database with literature evidence. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and intergenic correlation analysis was performed using the corrplot R software package. ZJW-regulated gene expression was verified by RT-qPCR. RESULTS: Huanglian and Wuzhu contain 19 and 4 compounds, respectively. Huang Lian targets 146 proteins, and Wu Zhu Yu targets 28 proteins based on evidence from the literature. ZJW regulates a range of biological processes associated with immune function, including cytokine signaling and Toll-Like Receptor 4 (TLR4) cascade. ZJW regulates malignant CRC cells, immune cells (including T-cells, B-cells, mast cells, NK/NKT cells, and myeloid cells), and other non-immune cells (including endothelial cells, enteric glial cells, and pericytes). We confirmed that ZJW significantly downregulated the expression of TIMP1 and MTDH. CONCLUSIONS: ZJW regulates a range of cells in the CRC microenvironment, including malignant CRC, immune cells, and stromal cells. In CRC cell lines, downregulation of TIMP1 and MTDH by ZJW may play an important role in the immunomodulation in CRC.

The Role of Microglia in Brain Metastases: Mechanisms and Strategies.

Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung cancer, and melanoma are at a high risk of developing brain metastases. However, the mechanisms underlying the brain metastatic cascade remain poorly understood. Microglia, one of the major resident macrophages in the brain parenchyma, are involved in multiple processes associated with brain metastasis, including inflammation, angiogenesis, and immune modulation. They also closely interact with metastatic cancer cells, astrocytes, and other immune cells. Current therapeutic approaches against metastatic brain cancers, including small-molecule drugs, antibody-coupled drugs (ADCs), and immune-checkpoint inhibitors (ICIs), have compromised efficacy owing to the impermeability of the blood-brain barrier (BBB) and complex brain microenvironment. Targeting microglia is one of the strategies for treating metastatic brain cancer. In this review, we summarize the multifaceted roles of microglia in brain metastases and highlight them as potential targets for future therapeutic interventions.

GLDC promotes colorectal cancer metastasis through epithelial-mesenchymal transition mediated by Hippo signaling pathway.

Cancer metastasis remains a major cause of death in cancer patients, and epithelial-mesenchymal transition (EMT) plays a decisive role in cancer metastasis. Recently, abnormal expression of Glycine Decarboxylase (GLDC) has been demonstrated in tumor progression, and GLDC is up-regulated in cancers, such as lung, prostate, bladder, and cervical cancers. However, the exact role of GLDC in colorectal cancer (CRC) progression remains to be elucidated. The aim of our study was to explore the role of GLDC in CRC metastasis. The GSE75117 database was used to investigate GLDC expression in tumor center and invasive front tissues and we found that GLDC expression levels were higher in the invasive front tissue. GLDC expression levels were negatively correlated with the prognosis of CRC patients. In vitro studies have showed that GLDC can promote invasion and migration of CRC cells by inhibiting the Hippo signaling pathway and regulating the EMT process. Blocking the Hippo signaling pathway with Verteporfin reduced the effect of GLDC on CRC metastasis. In vivo metastasis assays further confirmed that tail vein injection of GLDC+/+ cells induced more lung metastasis, compared to normal CRC cells. The results of this study suggest that GLDC promotes EMT through the Hippo signaling pathway, providing a new therapeutic target for CRC metastasis.

Predictors based on cuproptosis closely related to angiogenesis predict colorectal cancer recurrence.

Up to one-third of colorectal cancer (CRC) patients experience recurrence after radical surgery, and it is still very difficult to assess and predict the risk of recurrence. Angiogenesis is the key factor of recurrence as metastasis of CRC is closely related to copper metabolism. Expression profiling by microarray from two datasets in Gene Expression Omnibus (GEO) was selected for quality control, genome annotation, normalization, etc. The identified angiogenesis-derived and cuproptosis-related Long non-coding RNAs (lncRNAs) and clinical data were screened and used as predictors to construct a Cox regression model. The stability of the model was evaluated, and a nomogram was drawn. The samples were divided into high-risk and low-risk groups according to the linear prediction of the model, and a Kaplan-Meier survival analysis was performed. In this study, a model was established to predict the postoperative recurrence of colon cancer, which exhibits a high prediction accuracy. Furthermore, the negative correlation between cuproptosis and angiogenesis was validated in colorectal cancer cell lines and the expression of lncRNAs in vitro was examined.

The role of YAP1 in survival prediction, immune modulation, and drug response: A pan-cancer perspective.

Introduction: Dysregulation of the Hippo signaling pathway has been implicated in multiple pathologies, including cancer, and YAP1 is the major effector of the pathway. In this study, we assessed the role of YAP1 in prognostic value, immunomodulation, and drug response from a pan-cancer perspective. Methods: We compared YAP1 expression between normal and cancerous tissues and among different pathologic stages survival analysis and gene set enrichment analysis were performed. Additionally, we performed correlation analyses of YAP1 expression with RNA modification-related gene expression, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint regulator expression, and infiltration of immune cells. Correlations between YAP1 expression and IC50s (half-maximal inhibitory concentrations) of drugs in the CellMiner database were calculated. Results: We found that YAP1 was aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications, particularly m6A methylation. High expression of YAP1 was associated with poor survival outcomes in ACC, BLCA, LGG, LUAD, and PAAD. YAP1 expression was negatively correlated with the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, and positively correlated with the infiltration of myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in pan-cancer. Higher YAP1 expression showed upregulation of TGF-ß signaling, Hedgehog signaling, and KRAS signaling. IC50s of FDA-approved chemotherapeutic drugs capable of inhibiting DNA synthesis, including teniposide, dacarbazine, and doxorubicin, as well as inhibitors of hypoxia-inducible factor, MCL-1, ribonucleotide reductase, and FASN in clinical trials were negatively correlated with YAP1 expression. Discussion: In conclusion, YAP1 is aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications. High expression of YAP1 is associated with poor survival outcomes in certain cancer types. YAP1 may promote tumor progression through immunosuppression, particularly by suppressing the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, as well as recruiting MDSCs and CAFs in pan-cancer. The tumor-promoting activity of YAP1 is attributed to the activation of TGF-ß, Hedgehog, and KRAS signaling pathways. AZD2858 and varlitinib might be effective in cancer patients with high YAP1 expression.

Transgelin-2 Involves in the Apoptosis of Colorectal Cancer Cells Induced by Tanshinone-IIA.

Tanshinone IIA (TanIIA) is the main active ingredient in the fat-soluble components isolated from Salvia miltiorrhiza Bunge. Our previous studies have convincingly proved that TanIIA is an effective drug against human colorectal carcinoma cells. In order to further demonstrate the effect of TanIIA on CRC, we carried out exploratory research about it in vivo and in vitro. The results demonstrated that TanIIA were observably more effective than control group in preventing tumor growth, and it has increased the survival time. Cancer cells viability and proliferation were accompanied by concentration and time dependent decline reached with TanIIA. We found that TanIIA altered the morphology of cytoskeleton and it could obviously induce apoptosis of colorectal cancer cells and block the cells in the G0/G1 phase. TanIIA also increased phosphorylation of p38MAPK, upregulated ATF-2 expression and downregulated Transgelin-2 expression, which could be reversed by SB203580, a p38MAPK-specific inhibitor. Our results suggested that TanIIA could induce apoptosis of colorectal cancer and block the cells in G0/G1 phase involved in downregulating the expression of Transgelin-2 through p38MAPK signal pathway.

Microscale purification in support of high-throughput medicinal chemistry.

In recent years, successful assay miniaturization has enabled the exploration of synthesis scale reduction in pharmaceutical discovery. Miniaturization of pharmaceutical synthesis and purification allows a reduction in material consumption and shortens timelines, which ultimately reduces the cost per experiment without compromising data quality. Isolating and purifying the compounds of interest is a key step in the library synthesis process. In this manuscript we describe a high-throughput purification workflow in support of microscale (1-5 µmol or 0.5-2 mg) library synthesis. The optimized microscale purification system can routinely purify 384-well reaction plates with an analysis time of 4 min per sample. Instrument optimization, critical parameters such as column loading, delay time calibration, ultrafast pre- and post-purification analysis and library purification examples are provided.

Discovery and Preclinical Pharmacology of an Oral Bromodomain and Extra-Terminal (BET) Inhibitor Using Scaffold-Hopping and Structure-Guided Drug Design.

Inhibition of the bromodomain and extra-terminal (BET) family of adaptor proteins is an attractive strategy for targeting transcriptional regulation of key oncogenes, such as c-MYC. Starting with the screening hit 1, a combination of structure-activity relationship and protein structure-guided drug design led to the discovery of a differently oriented carbazole 9 with favorable binding to the tryptophan, proline, and phenylalanine (WPF) shelf conserved in the BET family. Identification of an additional lipophilic pocket and functional group optimization to optimize pharmacokinetic (PK) properties culminated in the discovery of 18 (BMS-986158) with excellent potency in binding and functional assays. On the basis of its favorable PK profile and robust in vivo activity in a panel of hematologic and solid tumor models, BMS-986158 was selected as a candidate for clinical evaluation.

A method to establish a chronic restraint stress mouse model with colorectal cancer xenografts.

Colorectal cancer (CRC) remains one of the most common clinical cancers of digestive tract. Recently, a large number of researches have shown that chronic stress can actively participate in the development of CRC. The proposed method successfully established the model of chronic stress mouse model with colorectal cancer.•Chronic restraint stress (CRS) was used to establish chronic stress model.•CRS was combined with a colorectal cancer xenografts model.•Behavioural tests and tumour growth were used to evaluate model construction.

Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment.

The tumor immune microenvironment plays a vital role in the metastasis of colorectal cancer. As one of the most important immune cells, macrophages act as phagocytes, patrol the surroundings of tissues, and remove invading pathogens and cell debris to maintain tissue homeostasis. Significantly, macrophages have a characteristic of high plasticity and can be classified into different subtypes according to the different functions, which can undergo reciprocal phenotypic switching induced by different types of molecules and signaling pathways. Macrophages regulate the development and metastatic potential of colorectal cancer by changing the tumor immune microenvironment. In tumor tissues, the tumor-associated macrophages usually play a tumor-promoting role in the tumor immune microenvironment, and they are also associated with poor prognosis. This paper reviews the mechanisms and stimulating factors of macrophages in the process of colorectal cancer metastasis and intends to indicate that targeting macrophages may be a promising strategy in colorectal cancer treatment.

Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear. PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms. METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored. RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling. CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.

PEG-poly(amino acid)s/EpCAM aptamer multifunctional nanoparticles arrest the growth and metastasis of colorectal cancer.

Tanshinone II-A (TSIIA) is a derivative of a phenanthrene-quinone extracted from a TCM herb, Salvia miltiorrhiza, and has been widely adopted in the treatment of colorectal cancer (CRC). It is known that TSIIA can lead to the apoptosis and differentiation of certain cell lines and it suppresses the proliferation and metastasis of tumors. However, its poor water solubility and low bioavailability when taken orally have prevented this drug being utilized effectively in the body. A nanoparticle (NP) drug carrier system is a technology that can effectively improve drug utilization and targeting ability. In this study, a new NP drug carrier system is reported: EpCAM targeting TSIIA-encapsulated poly(amino acid)s NPs (EpCAM-TSIIA-NPs). The results show that this new targeted NP drug carrier system has higher cytotoxicity, better water solubility and better targeting ability, and can effectively suppress the proliferation and metastasis of tumors. In addition, the invasion and metastasis mechanism of colorectal cancer (CRC) under ß-catenin nuclear meditation suppressed by EpCAM-TSIIA-NPs is also discussed. It is found that the immune-targeted type EpCAM-TSIIA-NPs could effectively enhance the expression of APC and axin when compared to normal NPs. It could improve the stability of ß-catenin destruction complex and suppress the occurrence and progression of tumors by stopping the nuclear activities of ß-catenin.

Driving Potency with Rotationally Stable Atropisomers: Discovery of Pyridopyrimidinedione-Carbazole Inhibitors of BTK.

Bruton's tyrosine kinase (BTK) has been shown to play a key role in the pathogenesis of autoimmunity. Therefore, the inhibition of the kinase activity of BTK with a small molecule inhibitor could offer a breakthrough in the clinical treatment of many autoimmune diseases. This Letter describes the discovery of BMS-986143 through systematic structure-activity relationship (SAR) development. This compound benefits from defined chirality derived from two rotationally stable atropisomeric axes, providing a potent and selective single atropisomer with desirable efficacy and tolerability profiles.

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer.

Transgelins, including transgelin-1 (T-1), transgelin-2 (T-2), and transgelin-3 (T-3), are a family of actin-binding proteins (ABPs) that can alter the structure and morphology of the cytoskeleton. These proteins function by regulating migration, proliferation and apoptosis in many different cancers. Several studies have shown that in various types of tumor cells, including colorectal cancer (CRC) cells, and in the tumor microenvironment, the expression and biological effects of transgelins are diverse and may transform during tumor progression. Previous researches have demonstrated that transgelin levels are positively correlated with metastasis in CRC, and down-regulating their expression can inhibit this process. In advanced disease, T-1 is a tumor activator with increasing expression, and T-2 expression increases with the progression of CRC. Finally, T-3 is only expressed in neurons and is not associated with CRC. This evidence suggests that T-1 and T-2 are potential biomarkers and therapeutic targets for CRC metastasis.

Xiaoyaosan slows cancer progression and ameliorates gut dysbiosis in mice with chronic restraint stress and colorectal cancer xenografts.

Depression is a risk factor for colorectal cancer (CRC) progression. Xiaoyaosan (XYS) is a traditional Chinese medicine prescription for treating depression. Our present study aimed to investigate the effect of XYS on chronic restraint stress (CRS) in mice with CRC xenografts and explore its underlying mechanisms. XYS treatment for 21 consecutive days successfully reduced the tumour volume and tumour weight in mice and prolonged the overall survival time. In addition, the intestinal permeability in the XYS group was significantly improved after administration. The 16S rRNA high-throughput sequencing method was used to sequence stool samples to check the structure and changes of gut bacteria. XYS mainly regulated the abundance of Bacteroides, Lactobacillus, Desulfovibrio and Rikenellaceae. Taken together, these results provide direct strong evidence that XYS effectively improves the progression of CRC in CRS-handled mice, and its efficacy is associated with the modulation of gut dysbiosis. The application of XYS can be a novel therapeutic strategy for CRC patients with depression.

Exosomes as Actively Targeted Nanocarriers for Cancer Therapy.

In recent years, it has been found that exosomes can be used as nanocarriers, which can be used in the treatment of tumors by carrying contents. The exosomes are derived from the secretion of the organism's own cells and are characterized by a phospholipid bilayer structure and a small particle size. These characteristics guarantee that the exosomes can carry a wide range of tumor drugs, deliver the drug to the cancer, and reduce or eliminate the tumor drug band. The toxic side effects were significantly eliminated; meanwhile, the therapeutic effects of the drug on the tumor were remarkably improved. This paper reviewed the strategies and drugs presented by different scholars for the treatment of tumors based on the drugs carried by exosomes.

How does self-esteem affect mobile phone addiction? The mediating role of social anxiety and interpersonal sensitivity.

Low self-esteem is an important factor influencing mobile phone addiction, which has been well documented. However, little research focused on the mechanism underlying the association between self-esteem and mobile phone addiction. We hypothesized that social anxiety and interpersonal sensitivity may mediate the relationship between self-esteem and mobile phone addiction. Six hundred and fifty three (353 girls among them) college students with the mean age of 19.94 (SD = 1.34) were recruited for the study. Participants completed mobile phone addiction scale, Rosenberg self-esteem scale, the social anxiety questionnaire and interpersonal sensitivity subscale of SCL-90. The findings were as follows: 1) interpersonal sensitivity mediated the relation between self-esteem and mobile phone addiction. 2) social anxiety and interpersonal sensitivity sequentially mediated the relation between self-esteem and mobile phone addiction. The result reveals that self-esteem has indirect effect on mobile phone addiction, which is mediated by social anxiety and interpersonal sensitivity.