Prospects and challenges of CAR-T cell therapy combined with ICIs.

Immune checkpoint molecules are a group of molecules expressed on the surface of immune cells that primarily regulate their immune homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology that realizes tumor-targeted killing by constructing synthetic T cells expressing specific antigens through biotechnology. Currently, CAR-T cell therapy has achieved good efficacy in non-solid tumors, but its treatment of solid tumors has not yielded the desired results. Immune checkpoint inhibitors (ICIs) combined with CAR-T cell therapy is a novel combination therapy with high expectations to defeat solid tumors. This review addresses the challenges and expectations of this combination therapy in the treatment of solid tumors.

Application value of whole exome sequencing in screening and identifying novel mutations of hypopharyngeal cancer.

The research on targeted therapy of hypopharyngeal cancer is very scarce. The discovery of new targeted driver genes will promote the progress of hypopharyngeal cancer therapy to a great extent. In our research, whole-exome sequencing in 10 patients with hypopharyngeal cancer was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. 8113 mutation sites in 5326 genes were identified after strict screening. We identified 72 pathogenic mutations in 53 genes according to the ACMG guidelines. Gene Ontology (GO) annotation and KEGG enrichment analysis show the effect of these genes on cancer. Protein-protein interaction (PPI) was analyzed by string online software. The validation results of the ualcan database showed that 22 of the 53 genes may be related to the poor prognosis of patients with hypopharyngeal cancer. RBM20 has the most significant correlation with hypopharyngeal cancer, and it is likely to be the driver gene of hypopharyngeal cancer. In conclusion, we found possible therapeutic targets for hypopharyngeal cancer, especially RBM20 and KMT2C. Our study provides a basis for the pathogenesis and targeted therapy of hypopharyngeal cancer.

Quantifying causal effects from observed data using quasi-intervention.

BACKGROUND: Causal inference is a crucial element within medical decision-making. There have been many methods for investigating potential causal relationships between disease and treatment options developed in recent years, which can be categorized into two main types: observational studies and experimental studies. However, due to the nature of experimental studies, financial resources, human resources, and patients' ethical considerations, researchers cannot fully control the exposure of the research participants. Furthermore, most existing observational research designs are limited to determining causal relationships and cannot handle observational data, let alone determine the dosages needed for medical research. RESULTS: This paper presents a new experimental strategy called quasi-intervention for quantifying the causal effect between disease and treatment options in observed data by using a causal inference method, which converts the potential effect of different treatment options on disease into computing differences in the conditional probability. We evaluated the accuracy of the quasi-intervention by quantifying the impact of adjusting Chinese patients' neutrophil-to-lymphocyte ratio (NLR) on their overall survival (OS) (169 lung cancer patients and 79 controls).The results agree with the literature in this study, consisting of nine papers on cohort studies on the NLR and the prognosis of lung cancer patients, proving that our method is correct. CONCLUSION: Taken together, the results imply that quasi-intervention is a promising method for quantifying the causal effect between disease and treatment options without clinical trials, and it could improve confidence about treatment options' efficacy and safety.

Risk Factors of Urinary Pathogenic Bacteria Infection after Benign Prostatic Hyperplasia Surgery and Curative Effect Analysis of Shuangdong Capsule Intervention.

Benign prostatic hyperplasia (BPH) is a common and frequently occurring disease in clinics, with the main manifestations including frequent micturition, urinary incontinence, dysuria, and endless urination. Transurethral resection of the prostate (TURP) is the main treatment for BPH, but some patients are prone to urinary tract infection after surgery, which affects the prognosis. Therefore, it is of great significance to study the pathogenic characteristics and risk factors of postoperative urinary-derived pathogenic bacteria infection in patients with BPH for the prevention and treatment of postoperative infection. In addition, the treatment of patients with this disease is also the focus of clinical attention. Long-term massive application of antibiotics can induce drug-resistant mutations of bacteria, so it is urgent to find an efficient and safe therapeutic scheme in clinics. However, traditional Chinese medicine (TCM) has a long history of treating urinary tract infections. Therefore, Shuangdong capsule, a traditional Chinese medicine preparation, was selected for the combined treatment in this study. The results showed that age, concomitant diabetes mellitus, and preoperative prophylactic application of antibiotics were the independent risk factors for postoperative urine-derived pathogenic infection in BPH patients. Clinical intervention for BPH patients with concomitant risk factors should be emphasized in clinical practice. The combined use of Shuangdong capsule and conventional western medicine can improve the clinical symptoms and inflammatory reactions of postoperative urine-derived pathogenic infection in BPH patients. Due to its exact curative effect and high safety, it is worthy of promotion. The clinical study registration number is M2022019.

Regulating the Expression of HIF-1α or lncRNA: Potential Directions for Cancer Therapy.

Previous studies have shown that tumors under a hypoxic environment can induce an important hypoxia-responsive element, hypoxia-induced factor-1α (HIF-1α), which can increase tumor migration, invasion, and metastatic ability by promoting epithelial-to-mesenchymal transition (EMT) in tumor cells. Currently, with the deeper knowledge of long noncoding RNAs (lncRNAs), more and more functions of lncRNAs have been discovered. HIF-1α can regulate hypoxia-responsive lncRNAs under hypoxic conditions, and changes in the expression level of lncRNAs can regulate the production of EMT transcription factors and signaling pathway transduction, thus promoting EMT progress. In conclusion, this review summarizes the regulation of the EMT process by HIF-1α and lncRNAs and discusses their relationship with tumorigenesis. Since HIF-1α plays an important role in tumor progression, we also summarize the current drugs that inhibit tumor progression by modulating HIF-1α.

The potential, analysis and prospect of ctDNA sequencing in hepatocellular carcinoma.

Background: The genome map of hepatocellular carcinoma (HCC) is complex. In order to explore whether circulating tumor cell DNA (ctDNA) can be used as the basis for sequencing and use ctDNA to find tumor related biomarkers, we analyzed the mutant genes of ctDNA in patients with liver cancer by sequencing. Methods: We used next-generation targeted sequencing technology to identify mutations in patients with liver cancer. The ctDNA from 10 patients with hepatocellular carcinoma (including eight cases of primary hepatocellular carcinoma and two cases of secondary hepatocellular carcinoma) was sequenced. We used SAMtools to detect and screen single nucleotide polymorphisms (SNPs) and insertion deletion mutations (INDELs) and ANNOVAR to annotate the structure and function of the detected mutations. Screening of pathogenic and possible pathogenic genes was performed using American College of Medical Genetics and Genomics (ACMG) guidelines. GO analysis and KEGG analysis of pathogenic and possible pathogenic genes were performed using the DAVID database, and protein-protein interaction network analysis of pathogenic and possible pathogenic genes was performed using the STRING database. Then, the Kaplan-Meier plotter database, GEPIA database and HPA database were used to analyse the relationship between pathogenic and possible pathogenic genes and patients with liver cancer. Results: Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples revealed 8,950 single nucleotide variation (SNV) mutations and 70 INDELS. The most commonly mutated gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. We compared these results to the COSMIC database and determined that ctDNA could be used for sequencing. According to the ACMG guidelines, we identified 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 HCC patients and performed GO analysis, KEGG analysis, and PPI network analysis. Through further analysis, four genes significantly related to the prognosis of liver cancer were identified. Conclusion: In this study, our findings indicate that ctDNA can be used for sequencing. Our results provide some molecular data for the mapping of genetic variation in Chinese patients with liver cancer, which enriches the understanding of HCC pathogenesis and provides new ideas for the diagnosis and prognosis of HCC patients.

Nasal Nanovaccines for SARS-CoV-2 to Address COVID-19.

COVID-19 is still prevalent around the globe. Although some SARS-CoV-2 vaccines have been distributed to the population, the shortcomings of vaccines and the continuous emergence of SARS-CoV-2 mutant virus strains are a cause for concern. Thus, it is vital to continue to improve vaccines and vaccine delivery methods. One option is nasal vaccination, which is more convenient than injections and does not require a syringe. Additionally, stronger mucosal immunity is produced under nasal vaccination. The easy accessibility of the intranasal route is more advantageous than injection in the context of the COVID-19 pandemic. Nanoparticles have been proven to be suitable delivery vehicles and adjuvants, and different NPs have different advantages. The shortcomings of the SARS-CoV-2 vaccine may be compensated by selecting or modifying different nanoparticles. It travels along the digestive tract to the intestine, where it is presented by GALT, tissue-resident immune cells, and gastrointestinal lymph nodes. Nasal nanovaccines are easy to use, safe, multifunctional, and can be distributed quickly, demonstrating strong prospects as a vaccination method for SARS-CoV-2, SARS-CoV-2 variants, or SARS-CoV-n.

ALDH1B1 predicts poor survival for locally advanced nasopharyngeal carcinoma patients.

Background: Distant metastasis and local recurrence remain the major reasons of treatment failure in locally advanced nasopharyngeal carcinoma (NPC). Therefore, exploring novel biomarkers for prognosis and sensitivity of radiotherapy in locally advanced NPC is crucial. This retrospective study evaluates the expression and prognostic value of aldehyde dehydrogenase 1B1 (ALDH1B1) for locally advanced NPC patients. Methods: Sixty-seven locally advanced NPC patients and 22 chronic nasopharyngitis patients between September 2012 to November 2016 at The First Affiliated Hospital of University of South China were enrolled in this study. The expression of ALDH1B1 in tumor tissues were detected by using immunohistochemistry (IHC). Results: Significant difference was observed between NPC groups and Pharyngitis tissues groups, and NPC groups has a higher ratio of high ALDH1B1 expression. ALDH1B1 expression were significantly associated with age and radiotherapy response. The Kaplan-Meier analysis indicated that patients with high ALDH1B1 expression had a poor prognosis both in overall survival (OS) and progression-free survival (PFS). Univariate analysis found that age, radiotherapy response and ALDH1B1 expression were correlated with OS. Besides, factors affecting PFS are radiotherapy response and ALDH1B1 expression. Multivariate analysis revealed that radiotherapy response and ALDH1B1 expression were the independent prognostic factors for OS, whereas radiotherapy response was for PFS. Conclusions: The expression of ALDH1B1 was correlated with age and radiotherapy response. Patients with high ALDH1B1 expression show a poor prognosis both in OS and DFS. ALDH1B1 expression were the independent prognostic factors for OS.

The effect of surgery plus intensity-modulated radiotherapy on treatment in laryngeal cancer: A clinical retrospective study.

PURPOSE: As a common head and neck tumor, laryngeal cancer has attracted heightened attention for its treatment and prognosis. Surgery and radiotherapy were mainly therapeutic approaches in laryngeal cancer, and intensity-modulated radiotherapy (IMRT) was a precision treatment way in radiotherapy. However, the therapeutic effect of surgery plus IMRT in laryngeal cancer was rarely reported. This study aims to determine the effect of IMRT on the treatment of patients with laryngeal cancer. METHODS: A total of 125 patients with laryngeal cancer were collected and retrospectively analyzed based on their clinical data and follow-up results. These patients had a clear treatment plan for surgery and intensity-modulated radiotherapy. RESULTS: Smoking, lymph node metastasis, TNM staging and therapeutic approaches could affect the survival of patients with laryngeal cancer. It was shown that the laryngeal function retention rate in the simple IMRT group was significantly higher than the simple surgery group and surgery plus IMRT group. The 5-year survival rate of surgery plus IMRT, simple surgery and simple IMRT were 82.86%, 53.85% and 43.33%, respectively. The locoregional recurrences rate of surgery plus IMRT, simple surgery and simple IMRT were 14.29%, 34.62% and 43.33%. CONCLUSION: Surgery plus IMRT was a feasible and efficacious treatment technique for patients with laryngeal cancer, which effectively prolong the survival time of patients.

Research Progress and Direction of Novel Organelle-Migrasomes.

Migrasomes are organelles that are similar in structure to pomegranates, up to 3 µm in diameter, and contain small vesicles with a diameter of 50-100 nm. These membranous organelles grow at the intersections or tips of retracting fibers at the back of migrating cells. The process by which cells release migrasomes and their contents outside the cell is called migracytosis. The signal molecules are packaged in the migrasomes and released to the designated location by migrasomes to activate the surrounding cells. Finally, the migrasomes complete the entire process of information transmission. In this sense, migrasomes integrate time, space, and specific chemical information, which are essential for regulating physiological processes such as embryonic development and tumor invasion and migration. In this review, the current research progress of migrasomes, including the discovery of migrasomes and migracytosis, the structure of migrasomes, and the distribution and functions of migrasomes is discussed. The migratory marker protein TSPAN4 is highly expressed in various cancers and is associated with cancer invasion and migration. Therefore, there is still much research space for the pathogenesis of migratory bodies and cancer. This review also makes bold predictions and prospects for the research directions of the combination of migrasomes and clinical applications.

Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy.

Abnormally alternative splicing events are common hallmark of diverse types of cancers. Splicing variants with aberrant functions play an important role in cancer development. Most importantly, a growing body of evidence has supported that alternative splicing might play a significant role in the therapeutic resistance of tumors. Targeted therapy and immunotherapy are the future directions of tumor therapy; however, the loss of antigen targets on the tumor cells surface and alterations in drug efficacy have resulted in the failure of targeted therapy and immunotherapy. Interestingly, abnormal alternative splicing, as a strategy to regulate gene expression, is reportedly involved in the reprogramming of cell signaling pathways and epitopes on the tumor cell surface by changing splicing patterns of genes, thus rendering tumors resisted to targeted therapy and immunotherapy. Accordingly, increased knowledge regarding abnormal alternative splicing in tumors may help predict therapeutic resistance during targeted therapy and immunotherapy and lead to novel therapeutic approaches in cancer. Herein, we provide a brief synopsis of abnormal alternative splicing events in cancer progression and therapeutic resistance.

Progress in the Understanding of the Mechanism of Tamoxifen Resistance in Breast Cancer.

Tamoxifen is a drug commonly used in the treatment of breast cancer, especially for postmenopausal patients. However, its efficacy is limited by the development of drug resistance. Downregulation of estrogen receptor alpha (ERα) is an important mechanism of tamoxifen resistance. In recent years, with progress in research into the protective autophagy of drug-resistant cells and cell cycle regulators, major breakthroughs have been made in research on tamoxifen resistance. For a better understanding of the mechanism of tamoxifen resistance, protective autophagy, cell cycle regulators, and some transcription factors and enzymes regulating the expression of the estrogen receptor are summarized in this review. In addition, recent progress in reducing resistance to tamoxifen is reviewed. Finally, we discuss the possible research directions into tamoxifen resistance in the future to provide assistance for the clinical treatment of breast cancer.

Down-regulation of PCK2 inhibits the invasion and metastasis of laryngeal carcinoma cells.

Laryngeal carcinoma is one of the common malignancies of head and neck. However, the pathogenesis of laryngeal cancer has been not completely clear. To identify the effects of hypoxia on the invasion, metastasis, and metabolism of laryngeal carcinoma, iTRAQ-labeling-with-LC-MS/MS analysis was performed to identify differentially expressed proteins of the SCC10A cells under hypoxia and normoxia, while metabolites were examined by metabolic profiling. 155 proteins and 180 metabolites were identified and the PCK2 protein was selected for validation by Western Blotting. Immunohistochemistry (IHC) was performed to analyze the expression of PCK2 in formalin-fixed paraffin-embedded (FFPE) tissue sections, including laryngeal squamous cell carcinoma tissues from various stages. Collectively, we report that down-regulation of PCK2 inhibits the invasion, migration, and proliferation of laryngeal cancer under hypoxia and down-regulation of PCK2 may be used as a new strategy for laryngeal cancer therapy.

Prolactin (PRL), placenta growth factor (PIGF) and nerve growth factor receptor (NGFR) as biomarkers for early diagnosis and prognosis in patients with esophageal squamous cell carcinoma (ESCC).

BACKGROUND: The purpose of this study was to investigate the expression and clinical significance of prolactin (PRL), placenta growth factor (PIGF) and nerve growth factor receptor (NGFR) in esophageal squamous cell carcinoma (ESCC). METHODS: PRL, PIGF and NGFR were selected through being screened normal human and esophageal cancer (EC) plasma by high-throughput protein chips. Subsequently, enzyme linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were used to detect the expression in ESCC and control group. Then, its clinical significance was statistically evaluated. RESULTS: The expression of PRL, PIGF and NGFR in plasma and tissue of patients with EC was higher than healthy controls and adjacent tissue, respectively. Among the clinical parameters, the expression of PRL and NGFR protein was correlated with the tumor classification of ESCC (P<0.05), while PIGF protein was correlated with the clinical stage of ESCC (P<0.05). The area under the ROC (AUC) of PRL, PIGF, and NGFR in plasma was 0.69, 0.72, and 0.66 in separately. Furthermore, the combined detection of three proteins had a better AUC of 0.74 with a sensitivity of 66.7% and a specificity of 72.4%. Kaplan-Meier survival analysis revealed that positive expression of PRL, PIGF and NGFR in histological predicted significantly worse overall survival (OS) than negative expression (P<0.05). CONCLUSIONS: PRL, PIGF and NGFR are promising biomarkers for diagnosis and prognosis prediction of ESCC.

Retracted Article: Synthesis of xanthone derivatives and anti-hepatocellular carcinoma potency evaluation: induced apoptosis.

Twenty-one xanthone derivatives (XDs) were synthesized by a microwave-assisted technique. Their in vitro inhibition potency against the growth of four cancer cell lines was evaluated. XD-1 ∼ [6,9,10-trihydroxy-3,3-dimethyl-5-(2-methylbut-3-en-2-yl)-3H,7H-pyrano[2,3-c]xanthen-7-one] was confirmed as the most active agent against HepG2 cell line growth with IC50 of 18.6 ± 2.31 µM. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for XD-1. XD-1 arrested HepG2 cells on the G0/G1 phase, as indicated by the decreased expressions of cyclin D and CDK2 and the increased expressions of p21. Western blot implied that XD-1 regulated p53/MDM2 to a better healthier state. Moreover, XD-1-induced cell apoptosis was mitochondrion-mediated, as evidenced by caspase activation and involved the PI3K/AKT/mTOR signaling pathway. All the evidence supports that XD-1 is a significant anti-cancer agent for HCC.

Overexpression of ATP5b promotes cell proliferation in asthma.

Asthma is a complicated systemic disease of the airways, which is characterized by variable symptoms, including bronchial hyper­responsive-ness, inflammation and airflow obstruction. The prevalence of asthma has increased 2­3­fold over recent decades in developed countries; however, the molecular mechanism of asthma remains unclear. In the current study, the expression of recombinant protein Dermatophagoides farinaeI (Derf I) was induced by isopropyl ß­D­1­thiogalactoside (IPTG) and purified using Ni­NTA. Derf I, an important antigen of asthma, was used to establish the animal model of asthma. Airway hyper­responsiveness was mea-sured using unrestrained whole­body plethysmography with a four­chamber system. Immunoglobulin (Ig)E, IgG and IgG2a were analyzed using indirect enzyme­linked immunosorbent assay (ELISA). Proteomic technology was applied to detect the difference between the normal lung tissue and asthma lung tissue samples of the asthma model. Cytokines in bronchoalveolar lavage fluid and the splenocyte culture medium were measured by ELISA and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to detect the mRNA expression of ATP synthase, H+ transporting, mitochondrial F1 complex, ß polypeptide (ATP5b). In addition, cell growth of arterial smooth muscle cells (ASMCs) was evaluated by MTT assay. In the current study, Derf I was successfully used to construct the animal model of asthma. Out of 23 proteins that exhibit 3­fold upregulation or downregulation, ATP5b was chosen for further investigation. The data indicated that ATP5b was overexpressed in the asthma lung tissue when compared with the normal lung tissue. However, when ATP5b was knocked down, cell growth decreased. Therefore, overexpressed ATP5b leads to airway smooth muscle cell (ASMC) proliferation and finally to ASM thickening. Thus, to the best of our knowledge, this is the first study to report that the expression level of ATP5b was markedly increased in lung tissue samples of an asthma model compared with the tissue samples from normal lungs, which promoted ASMC proliferation and contributed to airway remodeling.

The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism.

Hypoxia-inducible factor (HIF) is a main heterodimeric transcription factor that regulates the cellular adaptive response to hypoxia by stimulating the transcription of a series of hypoxia-inducible genes. HIF is frequently upregulated in solid tumors, and the overexpression of HIF can promote tumor progression or aggressiveness by blood vessel architecture and altering cellular metabolism. In this review, we focused on the pivotal role of HIF in tumor angiogenesis and energy metabolism. Furthermore, we also emphasized the possibility of HIF pathway as a potential therapeutic target in cancer.

The potential value of microRNA-4463 in the prognosis evaluation in hepatocellular carcinoma.

The purpose of this study is to measure the expression of microRNA-4463 and microRNA-6087 between normal persons and patients with hepatocellular carcinoma (HCC), and to clarify the meaning of them in the prognosis evaluation in HCC. Forty-five samples from healthy people and patients, who had been diagnosed with hepatocellular carcinoma before any treatment, were collected to study respectively. Real-time PCR was used to detect the expression of miRNA-4463 and miRNA-6087 in the serum of control group and hepatocellular carcinoma patients. The expression of miR-4463 in the serum of HCC patients was significantly higher than that in control group (P < 0.05), and the expression level was independent of gender, tumor size, cell types, stages, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and HBsAg status (P > 0.05). But there was a significant difference of different level of AFP in HCC (P < 0.05), and the difference between the group of AFP lower than 400 ug/l and the control group is statistically significant (P < 0.05). Besides, the survival time had showed a significant difference at the high and low expression levels (P < 0.05). But the expression level of miRNA-6087 was no difference in HCC and control group. The disorder of miRNA-4463 occurred in HCC, even the AFP level doesn't rises. What's more, patients who get the high level of miRNA-4463 seem to have a shorter survival time. And it contributes great to the prognostic evaluation. This is the first study to illustrate the potential significance of miRNA-4463 in the prognosis in HCC.

Overexpression of CXCR4 promotes invasion and migration of non-small cell lung cancer via EGFR and MMP-9.

The aim of the present study was to verify whether overexpression of CXC receptor 4 (CXCR4) promotes the invasion and migration of non-small cell lung cancer (NSCLC) via epidermal growth factor receptor (EGFR) and matrix metallopeptidase-9 (MMP-9), and to detect the association between CXCR4, EGFR and MMP-9. The effects of overexpression of CXCR4 on lung cancer cell functions were investigated by migration and invasion assays. Western blotting and zymograph assays were used to analyze the protein expression levels of EGFR and the production of MMP-9, respectively. Immunohistochemistry was applied to analyze the expression of EGFR, CXCR4 and MMP-9 in NSCLC. Statistical analyses were used to detect the associations among EGFR, CXCR4 and MMP-9 in NSCLC. Finally, survival analyses were performed. CXCR4 overexpression enhanced cell motility and invasion. CXCR4 also promoted expression of EGFR and elevated MMP-9 production. CXCR4, EGFR and MMP-9 were highly expressed in NSCLC, and were not identified as associated with age and sex (P>0.05). However, they were associated with tumor differentiation and lymph node metastasis (P<0.05). CXCR4, EGFR and CXCR4 expression were positively associated with one another in NSCLC (P<0.05). In addition, patients with positive expression of CXCR4, EGFR or MMP-9 in tumors exhibited significantly shorter overall survival compared with those with negative expression (P<0.05). In conclusion, CXCR4 overexpression enhanced cell motility and invasion via EGFR and MMP-9. CXCR4, EGFR and MMP-9 were identified as highly expressed in NSCLC, and there was positive correlation among them.

Bcl-2 overexpression contributes to laryngeal carcinoma cell survival by forming a complex with Hsp90ß.

Laryngeal carcinoma (LC) is one of the most common malignant tumors of all head and neck squamous cell carcinomas (HNSCCs). However, the molecular mechanism and genetic basis of the development of LC have not been fully elucidated. To explore the possible mechanism, targeted proteomic analysis was performed on Bcl-2-associated proteins from LC cells. According to our results, 35 proteins associated with Bcl-2 were identified and Hsp90ß was confirmed by co-immunoprecipitation and western blot analysis. Protein­protein interaction (PPI) analysis indicated that Bcl-2­Hsp90ß interactions may be involved in the anti-apoptotic progression of LC. Further results revealed that disruption of the Bcl-2-Hsp90ß interaction inhibited the anti-apoptotic ability of Bcl-2 and decreased the caspase activation in LC, which has broad implications for the better understanding of tumor formation, tumor cell survival and development of metastasis due to Bcl-2. Collectively, we report the mechanism by which Bcl-2 functions in LC as an anti-apoptotic factor in relation to its association with proteins and potentially identify a Bcl-2/Hsp90ß axis as a novel target for LC therapy.